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To evaluate the impact of the CD4 count on ESAT6-CFP10 (EC) skin test, QuantiFERON-TB Gold In-tube test (QFT) and tuberculin skin test (TST) in a large prison and communities in Jiangsu Province among people living with HIV (PLHIV). Participants in communities were tested with the QFT and EC skin test and in prison were tested with the QFT, TST and EC skin test. A 4-knotted restricted cubic spline fitted for Logistic models was used to explore the cutoff point of CD4 count and the associations between changes in CD4 count and Mycobacterium tuberculosis (M.tb) infection. Among 1,815 PLHIV included, 19.3% (350) were from prisons and 80.7% (1465) were identified through community screenings. M.tb infection rates were 12.2% and 8.3% through QFT and EC tests, respectively. Odd Ratios (ORs) for infection increased with CD4 counts, peaking at 618 cells/mm3 for EC, 392 cells/mm3 for QFT, then plateaued. However, the pattern differed for EC between prison and screening scenarios. In prison settings, M.tb infection increased with CD4 count from 0 to 350 cells/mm3, plateaued until 500 cells/mm3, and then persistently increased. Conversely, for community, ORs decreased until 300 cells/mm3, followed by an increase between 300 and 729 cells/mm3, after which they continued to rise persistently. Our cross-sectional study among PLHIV revealed a higher rate of M.tb infection in prison compared to the community. The relationship between CD4 count and infection became negative after a certain threshold. This pivotal point differed with detection methods, with QFT showing lower CD4 thresholds than EC. [ABSTRACT FROM AUTHOR]

Background: Idiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL. Case Presentation: We herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis. Conclusions: Nocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Reliable and ultra-fast DNA and RNA sequencing have been achieved with the emergence of high-throughput sequencing technology. When combining the results of DNA and RNA sequencing for tumor cells of cancer patients, neoantigens that potentially stimulate the immune response of either CD4+ or CD8+ T cells can be identified. However, due to the abundance of somatic mutations and the high polymorphic nature of human leukocyte antigen (HLA) it is challenging to accurately predict the neoantigens. Moreover, comparing to HLA-I presented peptides, the HLA-II presented peptides are more variable in length, making the prediction of HLA-II loaded neoantigens even harder. A number of computational approaches have been proposed to address this issue but none of them considers the DNA origin of the neoantigens from the perspective of 3D genome. Here we investigate the DNA origins of the immune-positive and non-negative HLA-II neoantigens in the context of 3D genome and discovered that the chromatin 3D architecture plays an important role in more effective HLA-II neoantigen prediction. We believe that the 3D genome information will help to increase the precision of HLA-II neoantigen discovery and eventually benefit precision and personalized medicine in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies of other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors have been discovered. Their functioning may provide an explanation for some of the events observed in severe COVID-19 that cannot be directly explained by the model in which ACE2 constitutes the central point of infection. Diabetes mellitus type 2 (T2D) can induce severe COVID-19 development. Although many mechanisms associated with ACE2 can lead to increased SARS-CoV-2 virulence in diabetes, proteins such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster of differentiation 4 (CD4), transferrin receptor (TfR), integrins α5β1/αvβ3, or ACE2 co-receptors neuropilin 2 (NRP2), vimentin, and even syalilated gangliosides may also be responsible for worsening the COVID-19 course. On the other hand, some others may play protective roles. Understanding how diabetes-associated mechanisms can induce severe COVID-19 via modification of virus receptor functioning needs further extensive studies. [ABSTRACT FROM AUTHOR]

In recent years, Raman spectroscopy has garnered growing interest in the field of biomedical research. It offers a non-invasive and label-free approach to defining the molecular fingerprint of immune cells. We utilized Raman spectroscopy on optically trapped immune cells to investigate their molecular compositions. While numerous immune cell types have been studied in the past, the characterization of living human CD3/CD28-stimulated T cell subsets remains incomplete. In this study, we demonstrate the capability of Raman spectroscopy to readily distinguish between naïve and stimulated CD4 and CD8 cells. Additionally, we compared these cells with monocytes and discovered remarkable similarities between stimulated T cells and monocytes. This paper contributes to expanding our knowledge of Raman spectroscopy of immune cells and serves as a launching point for future clinical applications. [ABSTRACT FROM AUTHOR]

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of lives, leading to significant morbidity and mortality. With >772 million cases and nearly seven million deaths reported worldwide to date, the development of vaccines has been a critical step in mitigating the impact of COVID-19. However, concerns have arisen regarding the potential for SARS-CoV-2 mRNA vaccination to trigger autoimmune diseases, including autoimmune hepatitis (AIH). The present single-center, retrospective study aimed to compare the clinical and pathological features of AIH in patients with or without a history of SARS-CoV-2 mRNA vaccination. A total of 72 patients with AIH were examined. Among them, 10 had received the SARS-CoV-2 mRNA vaccination prior to AIH onset. These patients exhibited more pronounced CD4+ T cell infiltration into the liver tissue compared with those who were unvaccinated. No significant differences in the levels of other liver enzymes, autoimmune antibodies, or CD8+ T cell infiltration were observed between the groups. Moreover, the AIH patients with a history of SARS-CoV-2 mRNA vaccination had more extensive CD4+ T cell infiltration in their liver tissues than the unvaccinated patients. These findings suggested that the immune response to SARS-CoV-2 mRNA vaccination may influence the pathogenesis of AIH, highlighting the need for further research into the relationship between SARS-CoV-2 mRNA vaccination and autoimmune liver diseases. Such studies will also help clarify the distinction between vaccine-induced liver injury and traditional AIH. [ABSTRACT FROM AUTHOR]

Consistent care is crucial for the health maintenance of people living with human immunodeficiency virus (HIV) (PWH). The coronavirus 2019 (COVID-19) epidemic disrupted patient care in New York City (NYC), yet few studies investigated the association between COVID-19 and viral load suppression in PWH in NYC. This study aims to assess how the COVID-19 pandemic impacted HIV viral load and CD4 + T-cell counts in PWH. Medical records of 1130 adult HIV patients who visited the Special Treatment and Research Health Center in Brooklyn, NY, between January 2019 and May 2023 were compared across three timeframes (pre-pandemic, January 1, 2019 to December 31, 2019; first pandemic phase, March 19, 2020 to December 31, 2020; and second pandemic phase, January 1, 2021 to May 11, 2023). Demographic and clinical variables (e.g. viral load and CD4 + T cell count) were assessed. About 40% of patients did not have routine laboratory monitoring during the first pandemic phase compared with pre-pandemic. The mean HIV viral load was higher during the second pandemic phase compared with pre-pandemic (p = 0.009). The percentages of patients with undetectable HIV viral load and numbers (mm3) of CD4 + T-cells were similar for all time periods. These findings indicate that the COVID-19 pandemic may have exacerbated challenges for individuals who already had barriers to medication adherence or access. However, most individuals remained consistently on their antiretrovirals throughout the pandemic. Further studies are warranted to determine how to mitigate the impact of future pandemics for the health of PWH. [ABSTRACT FROM AUTHOR]

Abstract To evaluate the impact of the CD4 count on ESAT6-CFP10 (EC) skin test, QuantiFERON-TB Gold In-tube test (QFT) and tuberculin skin test (TST) in a large prison and communities in Jiangsu Province among people living with HIV (PLHIV). Participants in communities were tested with the QFT and EC skin test and in prison were tested with the QFT, TST and EC skin test. A 4-knotted restricted cubic spline fitted for Logistic models was used to explore the cutoff point of CD4 count and the associations between changes in CD4 count and Mycobacterium tuberculosis (M.tb) infection. Among 1,815 PLHIV included, 19.3% (350) were from prisons and 80.7% (1465) were identified through community screenings. M.tb infection rates were 12.2% and 8.3% through QFT and EC tests, respectively. Odd Ratios (ORs) for infection increased with CD4 counts, peaking at 618 cells/mm3 for EC, 392 cells/mm3 for QFT, then plateaued. However, the pattern differed for EC between prison and screening scenarios. In prison settings, M.tb infection increased with CD4 count from 0 to 350 cells/mm3, plateaued until 500 cells/mm3, and then persistently increased. Conversely, for community, ORs decreased until 300 cells/mm3, followed by an increase between 300 and 729 cells/mm3, after which they continued to rise persistently. Our cross-sectional study among PLHIV revealed a higher rate of M.tb infection in prison compared to the community. The relationship between CD4 count and infection became negative after a certain threshold. This pivotal point differed with detection methods, with QFT showing lower CD4 thresholds than EC.

Introduction. The persistence of immune dysfunction during therapy has serious consequences for the health of HIV-infected people. Therefore, an important direction is the search for drugs that can reduce the inflammatory potential of the immune system and serve as an additional component of antiviral therapy. Aim ‒ to study the effect of the immunomodulatory drug Sodium deoxyribonucleate with iron complex (DNA-Na-Fe) on the expression of activation markers in MT-4 cells infected with HIV-1. Materials and methods. Expression levels of CD4, CD28, CD38, CD62L and HLA-DR proteins on the plasma membrane were measured in cells. To assess viral activity, the p24 protein was quantified by ELISA. Results and discussion. The two cell variants with different replicative activity were analyzed. Control cells, cells with DNA-Na-Fe, infected cells and infected cells with DNA-Na-Fe were tested. Based on the results obtained, it can be concluded that antiviral activity of the drug in MT-4 cells infected with HIV-1 is associated with immunomodulatory activity that enhances the expression of membrane proteins CD4, CD28, CD38 and CD62L. Diversity in the effect of DNA-Na-Fe on the studied surface proteins expression in two cell lines indicates that they depend on the characteristics of the combined molecular biological processes occurring in cells. And the increased effects observed in a system with changes in replicative activity assumes its active participation in virus replication at the stages of virus penetration and budding. Conclusion. Studies have shown that DNA-Na-Fe has antiviral and immunomodulatory activity.

Abstract Reliable and ultra-fast DNA and RNA sequencing have been achieved with the emergence of high-throughput sequencing technology. When combining the results of DNA and RNA sequencing for tumor cells of cancer patients, neoantigens that potentially stimulate the immune response of either CD4+ or CD8+ T cells can be identified. However, due to the abundance of somatic mutations and the high polymorphic nature of human leukocyte antigen (HLA) it is challenging to accurately predict the neoantigens. Moreover, comparing to HLA-I presented peptides, the HLA-II presented peptides are more variable in length, making the prediction of HLA-II loaded neoantigens even harder. A number of computational approaches have been proposed to address this issue but none of them considers the DNA origin of the neoantigens from the perspective of 3D genome. Here we investigate the DNA origins of the immune-positive and non-negative HLA-II neoantigens in the context of 3D genome and discovered that the chromatin 3D architecture plays an important role in more effective HLA-II neoantigen prediction. We believe that the 3D genome information will help to increase the precision of HLA-II neoantigen discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

Abstract Background Idiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL. Case Presentation We herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis. Conclusions Nocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL. Clinical trial number Not applicable.

Latar belakang. Human immunodeficiency virus / Acquired Immune Deficiency Syndrome pada anak merupakan masalah kesehatan global yang serius. Penurunan sistem imun yang diukur melalui nilai CD4 seringkali diperparah oleh status gizi yang buruk, yang dapat memengaruhi perkembangan penyakit dan kualitas hidup pasien. Studi tentang hubungan antara status gizi dan nilai CD4 pada anak dengan HIV/AIDS masih terbatas. Tujuan. Tujuan penelitian ini untuk mengetahui hubungan antara status gizi dengan nilai CD4 pada pasien anak dengan Sindrom Imunodefisiensi Akuisita. Metode. Penelitian ini menggunakan rancangan penelitian analitik observasional dengan penegakan potong lintang. Penelitian ini dilakukan pada bulan Maret 2023 – Juni 2023. Hasil. Sebanyak 36 pasien anak dengan Sindrom Imunodefisiensi Akuisita dilibatkan dalam penelitian ini. Berdasarkan analisis deskriptif, rerata usia pasien sebesar 9,25±2,99 tahun. Selain itu, sebagian besar pasien merupakan perempuan, yakni sebanyak 19 pasien (52,8%) sedangkan untuk pasien laki-laki sebanyak17 pasien (47,2%). Sebagian besar pasien memiliki nilai CD4 normal, yakni sebesar 27 pasien (75,0%), sedangkan pasien yang memiliki nilai CD4 rendah, yakni sebesar 9 pasien (25,0%). Hasil analisis Chi-square menunjukkan bahwa tidak terdapat hubungan yang signifikan antara status gizi dengan nilai CD4 pada pasien anak dengan Sindrom Imunodefisiensi Akuisita (p=0,079; two-tailed). Kesimpulan. Tidak terdapat hubungan yang signifikan antara status gizi dengan nilai CD4 pada pasien anak dengan Sindrom Imunodefisiensi Akuisita

Background: Neoadjuvant chemotherapy (NAC) is an integral component of modern treatment for invasive breast cancer with no special type (IBC-NST). The interaction between the immune system and cancer, particularly through immune-infiltrating lymphocytes (TIL), continues to be studied to understand how treatments like NAC influence the disease progression and response to various therapies. This study was designed to investigate changes in the pattern of CD4+ TIL infiltration before and after NAC. Methods: This retrospective cohort study involved 32 participants. NAC was administered for 3 months, comprising six cycles of chemotherapy. Variables such as age, tumor size, grade, lymphovascular invasion, and regional lymph node metastasis (RLNM) were evaluated. Furthermore, the expression of receptors, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER-2), and Ki-67 was evaluated. Infiltration of the tumor by CD4+ TILs was assessed using immunohistochemistry, whereas other data were retrieved from the medical records of the participants. Data were analyzed using R software. Results: There was a significant increase in CD4+ TIL infiltration after NAC administration. Before NAC treatment, there were significant associations between stromal CD4+ TIL with tumor size after NAC (P = 0.047), intratumoral CD4+ TIL with age (P = 0.031), and intratumoral CD4+ TIL with HER-2 status (P = 0.037). After NAC treatment, intratumoral CD4+ TIL was associated with tumor size before NAC (P = 0.009) and RLNM (P = 0.026). Conclusion: NAC is associated with a significant increase in CD4+ TIL infiltration in patients with IBC-NST.

Amyotrophic Lateral Sclerosis (ALS) is a poorly understood and fatal disease. It has a low prevalence and a 2–4 year survival period. Various theories and hypotheses relating to its development process have been proposed, albeit with no breakthrough in its treatment. Recently, the role of the adaptive immune system in ALS, particularly CD4+ T cells, has begun to be investigated. CD4+ T cells are a heterogeneous group of immune cells. They include highly pro-inflammatory types such as Th1 and Th17, as well as highly anti-inflammatory cells such as Tregs. However, the landscape of the role of CD4+ T cells in ALS is still not clearly understood. This review covers current hypotheses that elucidate how various CD4+ T cells can contribute to ALS development. These hypotheses include the SWITCH model, which suggests that, in the early stages of the disease, Tregs are highly capable of regulating the immune response. However, in the later stages of the disease, it seems that pro-inflammatory cells such as Th1 and Th17 are capable of overwhelming Treg function. The reason why this occurs is not known. Several research groups have proposed that CD4+ T cells as a whole might experience aging. Others have proposed that gamma delta T cells might directly target Tregs. Additionally, other research groups have argued that less well-known CD4+ T cells, such as Emoes+ CD4+ T cells, may be directly responsible for neuron death by producing granzyme B. We propose that the ALS landscape is highly complicated and that there is more than one feasible hypothesis. However, it is critical to take into consideration the differences in the ability of different populations of CD4+ T cells to infiltrate the blood–brain barrier, taking into account the brain region and the time of infiltration. Shedding more light on these still obscure factors can help to create a personalized therapy capable of regaining the balance of power in the battle between the anti-inflammatory and pro-inflammatory cells in the central nervous system of ALS patients.

Abstract Background Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. Methods Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. Results Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p

Fixation inhibits autolysis and is an essential step in disease. Our work examined how neutral buffer NBF (NBF), zinc formalin (ZF), and Bouin's fluid (BF) affected tissue specific CD4, CD68, and Pax8 anti-genetic determinants. Fifty-one sections were analyzed for each fixative marker. One hundred fifty-three portions were scored 0, 1, 2, and 3. The comparison between scores in the detection of CD4 epitopes reflects that BF fluid was significant compared to NBF and ZF at a level of p< 0.05, whereas NBF comes after ZF. Surprisingly, ZF has no significant scores in the context of CD4 detection. On the other hand, CD68 detection at the score one level revealed that NBF and ZF showed significant CD68 anti-genetic determinants, whereas none of the CD68 epitopes were significantly determined in BF fluid. Eventually, both NBF and BF produced an excellent determination of Pax8 epitopes in contrast to ZF. However, there is no significant difference between them. Regarding scores three comparisons in all fixatives, BF fluid showed high-quality CD4 marker expression in contrast to NBF and ZF; however, neither CD68 nor Pax8 showed any significance in this context. We conclude that NBF showed an excellent quality result in detecting all epitopes. However, BF fluid was supreme in detecting anti-genetic determinants of CD4 and Pax8 epitopes in score 3. Additionally, ZF could distinguish CD68 and Pax8 but failed to detect CD4. Conversely, no significant differences were recorded between both B and NBF.

Abstract Background In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage. Methods Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced). Results CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients. Conclusions TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.

Rituximab has been used to treat MS patients in Iceland for over a decade. However, long-term effect of rituximab on leukocyte populations has not yet been elucidated. By retrospective analysis of flow cytometric data from 349 patients visiting the neurological ward at The National University Hospital of Iceland from 2012 to 2023 for rituximab treatment, the long-term effect of rituximab and whether the effect was dose dependent (1000mg vs 500mg) was evaluated. No difference was detected in efficacy of B cell depletion in patients treated with 500mg as an initial dose of rituximab when compared to 1000mg. Long-term use of rituximab led to an increase in T cell count (p=0,0015) in patients receiving 3-8 doses of rituximab (1.5-8 years of treatment). The increase occurred in both CD4+ (p=0,0028) and CD8+ T cells (p=0,0015) and led to a decrease in the CD4/CD8 ratio (p=0,004). The most notable difference lies in reshaping the balance between näive and effector CD8+ T cells. The clinical implications of long-term treatment with rituximab and its effect on the T cell pool needs to be explored further. Since no difference in B cell depletion was detected between the two patient groups, 1000mg as an initial dose might be excessive, suggesting a personalized dosing regimen might have therapeutic and financial advantages. [ABSTRACT FROM AUTHOR]

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy. There is a critical lack of predictive biomarkers for patients with metastatic renal cell carcinoma receiving immunotherapy, therefore the identification of patients likely to benefit from this treatment represents a pressing clinical challenge. The Meet-URO 18 study is a multicentric, retrospective, translational study that delves into the immune tumor microenvironment (I-TME) of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line or beyond. Patients were categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Digital multitarget immunohistochemical analyses were performed on the I-TME of tumor samples of primary tumors or metastases. Primary analyses revealed that responders exhibited lower CD4 expression and higher levels of phosphorylated mTOR and CD56. Further extensive analysis of the I-TME focused on T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression assessed on tumor cells, and PD-L1 expression (SP263) assessed on both tumor and immune cells. Responders tumor tissue showed significantly lower CD4 expression, higher CD56 expression and a higher CD8/CD4 ratio compared with non-responders. Other parameters, including PD-L1 expression, did not reach statistical significance. This secondary analysis highlights the emerging significance of CD56 as a putative biomarker for immunotherapy, suggesting a critical role for regulatory CD4+ cells over cytotoxic CD8+ cells. [ABSTRACT FROM AUTHOR]

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. Methods: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. Results: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16− (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16− (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. Conclusion: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies. [ABSTRACT FROM AUTHOR]

Observational studies suggested that immune system disorder is associated with depression. However, the causal association has not been fully elucidated. Thus, we aim to assess the causality of the associations of immune cell profiles with risk of depression through Mendelian randomization analysis. We extracted genetic variances of immune cell traits from a large publicly available genome-wide association study (GWAS) involving 3757 participants and depression from a GWAS containing 246,363 cases and 561,190 controls of European ancestry. Inverse variance weighting (IVW) was performed as the MR primary analysis. Simultaneously apply MR-Egger and weighted median as supplementary enhancements to the final result. We further performed heterogeneity and horizontal pleiotropy test to validate the main MR results. Five immunophenotypes were identified to be significantly associated with depression risk: CD27 on IgD − CD38 dim B cell (OR = 1.019, 95 % CI = 1.010–1.028, P = 1.24 × 10−5), CD45RA − CD4 + T cell Absolute Count (OR = 0.974, 95 % CI = 0.962–0.986, P = 3.88 × 10−5), CD40 on CD14 − CD16 + monocyte (OR = 0.987, 95 % CI = 0.981–0.993, P = 2.1 × 10−4), CD27 on switched memory B cell (OR = 1.015, 95 % CI = 1.006–1.023, P = 2.6 × 10−4), CD27 on IgD − CD38 − B cell (OR = 1.017, 95 % CI = 1.008–1.027, P = 3.1 × 10−4). Our findings shed light on the intricate interaction pattern between the immune system and depression, offering a novel direction for researchers to investigate the underlying biological mechanisms of depression. • This study aims to explore the causality of the associations of immune cell profiles with risk of depression through Mendelian randomization analysis. • Five immunophenotypes were identified to be significantly associated with depression risk: CD27 on IgD- CD38dim B cell, CD45RA- CD4+ T cell Absolute Count, CD40 on CD14- CD16+ monocyte, CD27 on switched memory B cell, CD27 on IgD- CD38- B cell. • Our findings shed light on the intricate interaction pattern between the immune cells and depression, offering a novel direction for researchers to investigate the underlying biological mechanisms of depression. [ABSTRACT FROM AUTHOR]

This article discusses recent research on CD4 CAR T cells and their role in CAR T cell therapy (CTT). CD4 CAR T cells have traditionally been seen as providing support to CD8 CAR T cells, but recent studies have shown that CD4 CAR T cells can directly kill tumor cells and control their growth. However, CD4 CAR T cells have also been found to contribute to cytokine release syndrome (CRS), a serious adverse event in CTT. The article highlights the need for a deeper understanding of the roles and mechanisms of CD4 CAR T cells in order to design safer and more effective CAR T cell products. Additionally, the article discusses the impact of CD4 T cells on CAR T cell manufacturing, suggesting that co-culturing CD4 T cells with CD8 T cells can improve the quantity and quality of CAR T cells. The article concludes by emphasizing the importance of leveraging the benefits of CD4 T cells while minimizing their negative effects in CTT. [Extracted from the article]

Background: Study of expression of lymphocyte subsets could help to understand the pathophysiology of COVID-19 infection, development of novel treatment protocols and reducing rate of mortality among COVID-19 infected patients. The aim of this work was to correlate expression of lymphocyte subsets with the inflammatory markers and clinical status of patients with COVID-19 infection. Methods: This prospective study was performed at Zagazig University Isolation Hospitals and clinical pathology department, Zagazig, Egypt on 80 persons who were enrolled in this study; 40 COVID-19 patients with pneumonia made up group I, and the following individuals made up group II: 40 COVID-19 patients without pneumonia. Immunophenotyping of CD4 CD8 were measured by Flow Cytometry in both groups. Results: Patients had a considerable drop in CD4 CD8 levels with pneumonia than those without pneumonia Conclusions: Low levels of CD4 CD8 in COVID-19 patients are associated with a higher risk of pneumonia. [ABSTRACT FROM AUTHOR]

Immune cell function is impaired in hyperglycemic patients with diabetes but thought to improve with normalization of blood glucose levels. In this study, we hypothesized that this improvement might involve changes in T cell function. We compared the peripheral T cell markers between the people with and without type 2 diabetes (T2D) admitted to our hospital for glycemic control, and then in patients with T2D before and after the improvement of hyperglycemia by inpatient treatment. Expression of programmed death 1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (TIM-3), co-suppressive molecules, CD26 and CD28 on CD4-positive and/or CD8-positive T cells, the Th1/Th2 ratio, and the number of regulatory T cells (Tregs) were not significantly different between the people with and without T2D. Although an average of 10.6 days of inpatient treatment with improved hyperglycemia did not affect expression of PD-1 and TIM-3 in T cells, the Th1/Th2 ratio, or Tregs, it significantly reduced expression of CD26 and CD28 on CD4-positive T cells. CD26 and CD28 on CD4-positive T cells may be associated with the altered immune function after rapid improvement of hyperglycemia but that the other T-cell markers investigated here may not be. [ABSTRACT FROM AUTHOR]

Lack of access to resources is a "fundamental cause" of poor HIV outcomes across the care cascade globally and may have the greatest impact on groups with co-existing marginalized identities. In a sample of people living with HIV (PWH) who inject drugs and were not on antiretroviral therapy (ART), we explored associations between access to resources and HIV severity. Fundamental Cause Theory (FCT) sees socioeconomic status/access to resources as a root cause of disease and emphasizes that individuals with limited resources have fewer means to mitigate health risks and implement protective behaviors, which ultimately generates disparities in health outcomes. Guided by the FCT, we hypothesized that resource depletion (primary aim) and lower income (secondary aim) were associated with increased HIV severity. Using baseline data from the Linking Infectious and Narcology Care (LINC-II) trial of ART-naive PWH who inject drugs in St. Petersburg, Russia (n = 225), we examined the association between "past year resource runout" (yes vs. no) and "low-income (< 300 USD a month)" and the outcome HIV severity (CD4 count, continuous). We fit two separate linear regression models adjusted for gender, age, time since HIV diagnosis, and prior ART use. Participants had a mean age of 37.5 years and were 60% male. Two thirds (66%) reported resource depletion, and 30% had income below 300 USD a month. Average CD4 count was 416 cells/mm3 (SD 285). No significant association was identified between either resource depletion or low-income and HIV severity (adjusted mean difference in CD4 count for resource depletion: − 4.16, 95% CI − 82.93, 74.62; adjusted mean difference in CD4 count for low-income: 68.13, 95% CI − 15.78, 152.04). Below-average income and running out of resources were common among PWH who inject drugs and are not on ART in St. Petersburg, Russia. Resource depletion and low-income were not significantly associated with HIV disease severity as captured by CD4 count. The nuanced relationship between socioeconomic status and HIV severity among people with HIV who inject drugs and not on ART merits further examination in a larger sample. [ABSTRACT FROM AUTHOR]

Background: In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage. Methods: Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced). Results: CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients. Conclusions: TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients. [ABSTRACT FROM AUTHOR]

Background: The burden of advanced HIV disease remains a significant concern in sub-Saharan Africa. In 2015, the World Health Organization released recommendations to treat all people living with HIV (PLHIV) regardless of CD4 ("treat all") and in 2017 guidelines for managing advanced HIV disease. We assessed changes over time in the proportion of PLHIV with advanced HIV and their care cascade in two community settings in sub-Saharan Africa. Methods: Cross-sectional population-based surveys were conducted in Ndhiwa (Kenya) in 2012 and 2018 and in Eshowe (South Africa) in 2013 and 2018. We recruited individuals aged 15-59 years. Consenting participants were interviewed and tested for HIV at home. All participants with HIV had CD4 count measured. Advanced HIV was defined as CD4 < 200 cells/µL. Results: Overall, 6076 and 6001 individuals were included in 2012 and 2018 (Ndhiwa) and 5646 and 3270 individuals in 2013 and 2018 (Eshowe), respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 2012 (159/1376 (11.8%; 95% CI: 9.8-14.2)) to 2018 (53/1000 (5.0%; 3.8-6.6)). The proportion of individuals with advanced HIV on antiretroviral therapy (ART) was 9.1% (6.9-11.8) in 2012 and 4.2% (3.0-5.8) in 2018. In Eshowe, the proportion with advanced HIV was 130/1400 (9.8%; 8.0-11.9) in 2013 and 38/834 (4.5%; 3.3-6.1) in 2018. The proportion with advanced HIV among those on ART was 6.9% (5.5-8.8) in 2013 and 2.8% (1.8-4.3) in 2018. There was a significant increase in coverage for all steps of the care cascade among people with advanced HIV between the two Ndhiwa surveys, with all the changes occurring among men and not women. No significant changes were observed in Eshowe between the surveys overall and by sex. Conclusion: The proportion with advanced HIV disease decreased between the first and second surveys where all guidelines have been implemented between the two HIV surveys. Plain Language Summary: Distribution of advanced HIV disease between two time periods in Ndhiwa (Kenya) and Eshowe (South Africa) We examined changes over time in the proportion of people living with HIV (PLHIV) with advanced HIV and their care cascade in two community settings in sub-Saharan Africa: Ndhiwa (Kenya) and Eshowe (South Africa). In 2012 and 2018, a total of 6,076 and 6,001 individuals were included in Ndhiwa, and 5,646 and 3,270 individuals were included in Eshowe in 2013 and 2018, respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 11.8% in 2012 to 5.0% in 2018. The proportion of individuals with advanced HIV on antiretroviral therapy (ART) decreased from 9.1% in 2012 to 4.2% in 2018. In Eshowe, the proportion PLHIV with advanced HIV decreased from 9.8% in 2013 to 4.5% in 2018. Among those on ART, the proportion of PLHIV with advanced HIV decreased from 6.9% in 2013 to 2.8% in 2018. The results also showed a significant increase in coverage for all steps of the care cascade among people with advanced HIV in Ndhiwa in 2018 compared to 2012, with these changes observed only among men and not women. No significant changes were observed in Eshowe between the surveys, both overall and when comparing by sex. [ABSTRACT FROM AUTHOR]

Background:Tuberculosis (TB) patients with HIV/AIDS experience higher mortality rates, lower cure rates, and poorer treatment adherence compared to TB patients without HIV. As a result, TB can exacerbate HIV progression and lead to increased mortality. This study aims to investigate and summarize the determinants of TB incidence among people living with HIV/AIDS. Objective:This study employs a scoping review approach to explore the key factors associated with TB occurrence in HIV/AIDS patients. Methods:A literature search was conducted across indexed databases, including Scopus, PubMed, Google Scholar, and Crossref. Studies published between 2013 and 2021 were selected based on article titles, study design, population, intervention, and results. Fourteen relevant articles were included. Data were processed by identifying key sentences relevant to the coding framework, highlighting important findings, and organizing a narrative review framework. Qualitative data analysis was performed using NVIVO-12 Plus, with data presentation and report compilation. Results:The study identifies age, gender, education and knowledge level, nutritional status, use of antiretroviral therapy (ART), and cluster of differentiation 4 (CD4) cell count as the dominant factors influencing TB incidence among people living with HIV/AIDS. Conclusion:HIV infection weakens the immune system by attacking lymphocytes, leaving individuals with HIV/AIDS highly susceptible to Mycobacterium tuberculosis infection. Keywords:tuberculosis; HIV; AIDS; ART; CD4

BACKGROUND: Alcohol use has been linked to worse human immunodeficiency virus (HIV) immunologic/virologic outcomes, yet few studies have explored the effects of alcohol use disorder (AUD). This study assessed whether AUD severity is associated with HIV viral suppression and CD4 count in the three cohorts of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium. METHODS: People with HIV (PWH) in Uganda (n = 301), Russia (n = 400), and Boston (n = 251), selected in-part based on their alcohol use, were included in analyses. Logistic and linear regressions were used to assess the cross-sectional associations between AUD severity (number of DSM-5 diagnostic criteria) and (1) HIV viral suppression, and (2) CD4 count (cells/mm3 ) adjusting for covariates. Analyses were conducted separately by site. RESULTS: The proportion of females was 51% (Uganda), 34% (Russia), and 33% (Boston); mean age (SD) was 40.7 (9.6), 38.6 (6.3), and 52.1 (10.5), respectively. All participants in Uganda and all but 27% in Russia and 5% in Boston were on antiretroviral therapy. In Uganda, 32% met criteria for AUD, 92% in Russia, and 43% in Boston. The mean (SD) number of AUD criteria was 1.6 (2.4) in Uganda, 5.6 (3.3) in Russia, and 2.4 (3.1) in Boston. Most participants had HIV viral suppression (Uganda 92%, Russia 57%, Boston 87%); median (IQR) CD4 count was 673 (506, 866), 351 (201, 542), and 591 (387, 881), respectively. In adjusted models, there were no associations between AUD severity and HIV viral suppression: adjusted odds ratios (AOR) (95%CI) per 1 additional AUD criterion in Uganda was 1.08 (0.87, 1.33); Russia 0.98 (0.92, 1.04); and Boston 0.95 (0.84, 1.08) or CD4 count: mean difference (95%CI) per 1 additional criterion: 5.78 (-7.47, 19.03), -3.23 (-10.91, 4.44), and -8.18 (-24.72, 8.35), respectively. CONCLUSIONS: In three cohorts of PWH, AUD severity was not associated with HIV viral suppression or CD4 count. PWH with AUD in the current era of antiretroviral therapy can achieve virologic control.

Abstract Background A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented. Results To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001). Conclusions By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.

Background: Human papillomavirus is an infection that causes malignancy because of persistency and modulation of apoptotic pathways, especially caspase-3. Factors that can increase persistency, recurrency, and malignancy of HPV infection include HIV infection with low CD4 levels. There is disagreement or deep molecular understanding of the induction and modulation of apoptosis in HIV-mediated CD4+ T cell depletion, especially in CA. However, it is necessary to see how CD4+ levels can influence caspase-3, so it may open up new avenues for supporting investigation to consider the presence of malignancy or therapeutic strategies regarding CD4+ can induce apoptosis. Purpose: This study aimed to determine whether there is a correlation between CD4+ levels and caspase-3 expression in condyloma acuminata with HIV reactive patients. Methods: This is an analytic observational study with a cross-sectional design. The research was conducted at Dr. Moewardi General Hospital from August to December 2023. Nineteen patients with condyloma acuminata and HIV reactive were included in this study with a consecutive sampling technique. The expression of caspase-3 was assessed using immunohistochemical staining, looking at the percentage of stained cell nuclei and cytoplasm and CD4+ levels with flow cytometry examination—data analysis using Pearson correlation. Results: Respondents in this study were primarily men, self-employed with heterosexual orientation and genito-genital-oral sexual intercourse. The statistical analysis showed no significant relationship (p: 0.300, r: -0.251) between CD4+ levels and caspase-3 expression. Conclusions: While not statistically significant, CD4+ level is reduced in correlation with increased caspase-3 expressions.

We report a case of a 54-year-old female diagnosed with HIV and antiretroviral therapy (ART) for the same. Seven years ago, she suffered from fever, cough and weight loss, was diagnosed with pulmonary tuberculosis and also seropositive for HIV. She suffered from Herpes Zoster infection, after which her ART regimen was changed to TLD (tenofovir, lamivudine and dolutegravir). The patient presented with two episodes of pyoderma gangrenosum (PG), which were biopsy-proven, corresponding to a rise in CD4 counts above 500. She responded to glucocorticoids, both systemic and topical.

Abstract Background Antiretroviral Therapy (ART) is pivotal in extending the lives of people living with HIV (PLWH) and minimizing transmission. Rapid ART initiation, defined as commencing ART within seven days of HIV diagnosis, is recommended for all PLWH. Method A retrospective cohort study was conducted using data from the China Information System for Disease Control and Prevention. This study included PLWH diagnosed between January 2018 and December 2021 and treated by December 2022. Factors influencing rapid ART initiation were examined using univariate and multivariate Cox regression analyses. Results The study analyzed 1310 cases. The majority were male (77.4%), over 50 years old (46.7%), and contracted HIV through heterosexual transmission (70.0%). Rapid ART initiation was observed in 36.6% (n = 479) of cases, with a cumulative treatment rate of 72.9% within 30 days post-diagnosis. Heterosexual contact was associated with longer intervals from diagnosis to treatment initiation compared to homosexual contact (Adjusted Hazard Ratio (HR) = 0.813, 95% Confidence Interval (CI): 0.668–0.988). Individuals older than 50 years (Adjusted HR = 1.852, 95%CI: 1.149–2.985) were more likely to initiate ART rapidly. Conversely, treatment at the Second Public Hospital (Adjusted HR = 0.483, 95% CI: 0.330–0.708) and a CD4 cell counts above 500 (Adjusted HR = 0.553, 95% CI: 0.332–0.921) were associated with a lower likelihood of initiating treatment within seven days. Conclusions A higher CD4 cell counts and receiving care in local public hospitals may deter rapid ART initiation. Providing CD4 counts results at diagnosis and offering testing and treatment in the same facility could enhance the rate of rapid ART initiation.

CD4 T helper cells are an important group of cells in the immune system of vertebrates and express CD4 receptor on the cell surface. In mammals, the CD4 receptor is encoded by a single copy gene, whilst in fish, two copies of cd4 genes, namely cd4-1 and cd4-2, are found. In this study, the ectodomains of grass carp (Ctenopharyngodon idella, Ci) CD4-1 and CD4-2 were expressed in the E. coli cells and used to generate monoclonal antibodies in mice. Western blotting, confocal microscopy and flow cytometry were performed to characterize the monoclonal antibodies. It has been shown that the CiCD4-1 and CiCD4-2 monoclonal antibodies had good specificity to react with the recombinant ectodomains of CiCD4-1 and CiCD4-2 expressed in the CHO–S cells and the native CD4 molecules of grass carp. The CiCD4-1 monoclonal antibody did not recognize CiCD4-2 and verse versa. In addition, the CD4-1 and CD4-2 monoclonal antibodies specifically recognized the CD4-1 and CD4-2 receptors expressed in the HEK293 cells and native molecules of fish cells. Further, the percentages of lymphocytes in immune tissues of healthy fish were analyzed by flow cytometry. It was found that 17.6% of lymphocytes were CD4-1+ cells and 22.5% were CD4-2+ in the head kidney. In the spleen, 13.1% of lymphocytes were CD4-1+ and 18.6% were CD4-2+ while 7.3% of blood lymphocytes were CD4-1+ cells and 8.8% were CD4-2+ cells. The availability of the CD4-1 and CD4-2 monoclonal antibodies provides antibody-based tools for further elucidation of the functions of CD4 T cells in grass carp.

We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At weeks 24 and 48, ≥80% had CD4 ≥1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants.Clinical trials registrationNCT02140255.

Introduction: Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment. Materials and methods: The current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics. Results: There was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL- 38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients. Conclusion: These findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa. [ABSTRACT FROM AUTHOR]

Background: A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented. Results: To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001). Conclusions: By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis C virus (HCV)/HIV co‐infection has been identified as a risk for impaired CD4+ T‐cell recovery, possibly mediated by HCV‐induced liver fibrosis and/or immune activation. As HCV direct‐acting antivirals (DAAs) may partially reverse liver fibrosis and immune activation, sustained HCV virological response (SVR) may lead to improved CD4 recovery. We explored the effect of HCV DAA‐induced SVR on CD4 recovery among patients living with both HCV and HIV, including those with poor CD4 recovery on antiretroviral therapy (immunological non‐responders [INRs]). Methods: Subjects aged ≥18 years living with both HIV and HCV who achieved SVR with DAA were included. Pre‐DAA CD4 counts were included only after sustained HIV viral suppression and HIV viral suppression was maintained for the duration of the study. Segmented regression of interrupted time series analysis was used to evaluate changes in median CD4 count in the pre‐DAA period (−36 months) versus the post‐DAA period (+36 months). Results: In total, 156 patients were included. In the full cohort, median CD4 counts increased by 15% (p = 0.002) in the 6‐month period following DAA initiation, whereafter CD4 counts decreased by 2.7% per 6‐month period (p = 0.004). Among the 13 INRs, there was no immediate effect on median CD4 in the first 6 months after DAA initiation, whereafter there was a sustained CD4 increase (4.1% per 6‐month time interval [p = 0.02]). In total, 54% of INRs recorded a post‐DAA CD4 count of >350 cells/mm3. Conclusions: Successful DAA therapy induced a modest immediate CD4 immunological reconstitution among this cohort of patients living with both HIV and HCV, although this effect waned with time. By contrast, among INRs, achieving HCV SVR led to slower but sustained CD4 count recovery. [ABSTRACT FROM AUTHOR]

T cells are adaptive immune cells essential in pathogenic response, cancer, and autoimmune disorders. During the integration of biomaterials with host tissue, T cells modify the local inflammatory environment by releasing cytokines that promote inflammatory resolution following implantation. T cells are vital for the modulation of innate immune cells, recruitment and proliferation of mesenchymal stem cells (MSCs), and formation of functional tissue around the biomaterial implant. We have demonstrated that deficiency of αβ T cells promotes macrophage polarization towards a pro-inflammatory phenotype and attenuates MSC recruitment and proliferation in vitro and in vivo. The goal of this study was to understand how CD4+ and CD8+ T cells, subsets of the αβ T cell family, impact the inflammatory response to titanium (Ti) biomaterials. Deficiency of either CD4+ or CD8+ T cells increased the proportion of pro-inflammatory macrophages, lowered anti-inflammatory macrophages, and diminished MSC recruitment in vitro and in vivo. In addition, new bone formation at the implantation site was significantly reduced in T cell-deficient mice compared to T cell-competent mice. Deficiency of CD4+ T cells exacerbated these effects compared to CD8+ T cell deficiency. Our results show the importance of CD4+ and CD8+ T cells in modulating the inflammatory response and promoting new bone formation in response to modified Ti implants. CD4+ and CD8+ T cells are essential in modulating the peri-implant microenvironment during the inflammatory response to biomaterial implantation. This study shows that deficiency of either CD4+ or CD8+ T cell subsets altered macrophage polarization and reduced MSC recruitment and proliferation at the implantation site. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: The Human Immunodeficiency Virus (HIV) undermines the immune system, compromising the body's ability to fend off infections and certain cancers. This virus leads to the destruction and malfunction of immune cells, causing those infected to progressively suffer from immunodeficiency. Typically, the functioning of the immune system is assessed through the count of CD4 cells. Materials and Methods: A hospital-based observational cross-sectional study design was adopted. 150 patients were selected through systematic random sampling from January 2023 to December 2023. Patients who were known cases of HIV or recently diagnosed and presented in the Department of Medicine and all ART clients who attended the ART clinic in the Department of General Medicine at a Tertiary care Hospital in Hyderabad were included in the study considering the inclusion and exclusion criteria. Results: The majority of the study participants who were on ART and had anxiety and depression were females, 37.14%, compared to males, 27.7%. The majority of study participants having anxiety and depression were illiterate, 39.43%, followed by those with primary plus secondary schooling, 28.35%, graduates, 20.68%, and postgraduates, 11.6%. Conclusion: 30% of individuals reported clinical features of anxiety, depression, and mixed features of both. Female patients were more affected than male patients. Participants who were on less than 1 year of ART duration had the maximum depression, anxiety, and combined features of both. Highly depressed patients reported lower levels of CD4 count at the beginning. The treatment year of the patients was positively associated with a higher CD4 count at present; the duration of the ART regimen was associated with a high level of CD4 count at present. Therefore, early psychiatric intervention, psychological assessment, and treatment for depression or anxiety must be initiated to ensure better coping, treatment, and long-term compliance for ART in people living with HIV. [ABSTRACT FROM AUTHOR]

The choice of developing thymocytes to become CD8+ cytotoxic or CD4+ helper T cells has been intensely studied, but many of the underlying mechanisms remain to be elucidated. Recent multiomics approaches have provided much higher resolution analysis of gene expression in developing thymocytes than was previously achievable, thereby offering a fresh perspective on this question. Focusing on our recent studies using CITE-seq (cellular indexing of transcriptomes and epitopes) analyses of mouse thymocytes, we present a detailed timeline of RNA and protein expression changes during CD8 versus CD4 T cell differentiation. We also revisit our current understanding of the links between T cell receptor signaling and expression of the lineage-defining transcription factors ThPOK and RUNX3. Finally, we propose a sequential selection model to explain the tight linkage between MHC-I versus MHC-II recognition and T cell lineage choice. This model incorporates key aspects of previously proposed kinetic signaling, instructive, and stochastic/selection models. [ABSTRACT FROM AUTHOR]

Incidence of anal carcinoma (AC) in people living with HIV (PLWH) is increased compared to the general population. Adverse effects of chemoradiotherapy (CRT) on the immune system are associated with a significant detrimental prognosis on overall survival in patients receiving CRT for solid tumors. The aim of this study was to evaluate immunological factors, in particular the differences in recovery of CD4+ and CD8+ cell counts before and after CRT for AC in PLWH. Retrospective single-center chart review extraction to analyze immunological data collected from PLWH with AC; descriptive statistics were used. Thirty-six PLWH with histologically proven AC were included in the analysis. Absolute CD4 cell count 60 months after CRT was 67.2% of the value at the beginning of CRT, whereas the CD8 cell count reached 82.3%. These differences were statistically significant (p = .048), whereas CD4/CD8-ratio remained stable. The findings of the presented study regarding CD4+ and CD8+ cell recovery after CRT are congruent with results from prior studies in non-HIV infected patients. Although not reaching the level of prior CRT T cell numbers, the ability to generate CD8+ cells seems to be better recovered, while CD4+ regeneration is more impaired. These observations are best explained by faster recovery of CD8+ cells via thymic-independent pathways, which are not available for regeneration of CD4+ cells. Further studies with larger numbers of patients are required to analyze the specific CD4+ and CD8+ cell subsets. [ABSTRACT FROM AUTHOR]

Lactobacillus probiotic enriched diets can modulate host immune response. In this study, we investigated whether the three species Lactobacillus plantarum, L. bulgaricus and L. rhamnosus up-regulated two T-cells specific antigens and exerted the protective effect when administrated with formalin-killed Streptococcus agalactiae in Nile tilapia. For this purpose, a total of 180 Nile tilapia (average body weight 45.8 ± 22 g) were randomly divided into 6 experimental groups, i.e.: one control group and 5 vaccinated groups: Formalin killed cell (FKC); FKC+ Adjuvant; FKC+ L. plantarum; FKC+ L. bulgaricus and FKC+ L. rhamnosus. All groups were fed with normal commercial pellets and three groups were fed with pellets sprayed with three different lactobacilli. The results showed that the survival rate in the groups of Formalin killed cell (FKC) combined with oral administration of lactobacilli was from 70.0% to 75.0%. Protection in the control group amounted to 31.3% illustrating a significant difference with other experimental groups. In this research, gene expression of CD4 and CD8 which have essential functions in the immune response quantified by qRT-PCR in the head kidney, skin, and spleen was reported in the form of fold change. The analysis of fold change (Mean ± SD) related to CD4 and CD8 at 30- and 60-days post-immunization (dpi) respectively showed an increase in fold change in all probiotic groups compared to the FKC group in two of which it was significant at the level of p<0.05. The results revealed that vaccination with FKC administrated lactobacilli-enriched diets increased the expression of genes related to immune response which can indicate higher protection against Streptococcus agalactiae in the probiotic groups compared with FKC vaccination alone similar to the results observed in FKC coupled with adjuvant vaccination. [ABSTRACT FROM AUTHOR]

Background: Individual T cell responses vary significantly based on the microenvironment present at the time of immune response and on prior induced T cell memory. While the cecal ligation and puncture (CLP) model is the most commonly used murine sepsis model, the contribution of diverse T cell responses has not been explored. We defined T cell subset responses to CLP using single-cell RNA sequencing and examined the effects of prior induced T cell memory (Immune Education) on these responses. We hypothesized that Immune Education prior to CLP would alter T cell responses at the single cell level at a single, early post-CLP time point. Methods: Splenic T cells were isolated from C57BL/6 mice. Four cohorts were studied: Control, Immune-Educated, CLP, and Immune-Educated CLP. At age 8 weeks, Immune-Educated and Immune-Educated CLP mice received anti-CD3? antibody; Control and CLP mice were administered an isotype control. CLP (two punctures with a 22-gauge needle) was performed at 12-13 weeks of life. Mice were sacrificed at baseline or 24-hours post-CLP. Unsupervised clustering of the transcriptome library identified six distinct T cell subsets: quiescent naïve CD4+, primed naïve CD4+, memory CD4+, naïve CD8+, activated CD8+, and CD8+ cytotoxic T cell subsets. T cell subset specific gene set enrichment analysis and Hurdle analysis for differentially expressed genes (DEGs) were performed. Results: T cell responses to CLP were not uniform - subsets of activated and suppressed T cells were identified. Immune Education augmented specific T cell subsets and led to genomic signatures favoring T cell survival in unoperated and CLP mice. Additionally, the combination of Immune Education and CLP effected the expression of genes related to T cell activity in ways that differed from CLP alone. Validating our finding that IL7R pathway markers were upregulated in Immune-Educated CLP mice, we found that Immune Education increased T cell surface IL7R expression in post-CLP mice. Conclusion: Immune Education enhanced the expression of genes associated with T cell survival in unoperated and CLP mice. Induction of memory T cell compartments via Immune Education combined with CLP may increase the model's concordance to human sepsis. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral Therapy (ART) is pivotal in extending the lives of people living with HIV (PLWH) and minimizing transmission. Rapid ART initiation, defined as commencing ART within seven days of HIV diagnosis, is recommended for all PLWH. Method: A retrospective cohort study was conducted using data from the China Information System for Disease Control and Prevention. This study included PLWH diagnosed between January 2018 and December 2021 and treated by December 2022. Factors influencing rapid ART initiation were examined using univariate and multivariate Cox regression analyses. Results: The study analyzed 1310 cases. The majority were male (77.4%), over 50 years old (46.7%), and contracted HIV through heterosexual transmission (70.0%). Rapid ART initiation was observed in 36.6% (n = 479) of cases, with a cumulative treatment rate of 72.9% within 30 days post-diagnosis. Heterosexual contact was associated with longer intervals from diagnosis to treatment initiation compared to homosexual contact (Adjusted Hazard Ratio (HR) = 0.813, 95% Confidence Interval (CI): 0.668–0.988). Individuals older than 50 years (Adjusted HR = 1.852, 95%CI: 1.149–2.985) were more likely to initiate ART rapidly. Conversely, treatment at the Second Public Hospital (Adjusted HR = 0.483, 95% CI: 0.330–0.708) and a CD4 cell counts above 500 (Adjusted HR = 0.553, 95% CI: 0.332–0.921) were associated with a lower likelihood of initiating treatment within seven days. Conclusions: A higher CD4 cell counts and receiving care in local public hospitals may deter rapid ART initiation. Providing CD4 counts results at diagnosis and offering testing and treatment in the same facility could enhance the rate of rapid ART initiation. [ABSTRACT FROM AUTHOR]

Backround: Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T‐ and B‐cell levels change during carcinogenesis and whether such changes influence disease progression. Methods: The study used a retrospective sample of 73 prostate cancer cases (45 whites and 28 African Americans) that underwent surgery as their primary treatment and had a benign prostate biopsy at least 1 year before diagnosis. CD3+, CD4+, and CD20+ lymphocytes were quantified by immunohistochemistry in paired pre‐ and post‐diagnostic benign prostate biopsy and tumor surgical specimens, respectively. Clusters of similar trends of expression across two different timepoints and three distinct prostate regions—benign biopsy glands (BBG), tumor‐adjacent benign glands (TAG), and malignant tumor glandular (MTG) regions—were identified using Time‐series Anytime Density Peaks Clustering (TADPole). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of time to biochemical recurrence associated with region‐specific lymphocyte counts and regional trends. Results: The risk of biochemical recurrence was significantly reduced in men with an elevated CD20+ count in TAG (HR = 0.81, p = 0.01) after adjusting for covariates. Four distinct patterns of expression change across the BBG‐TAG‐MTG regions were identified for each marker. For CD20+, men with low expression in BBG and higher expression in TAG compared to MTG had an adjusted HR of 3.06 (p = 0.03) compared to the reference group that had nominal differences in CD20+ expression across all three regions. The two CD3+ expression patterns that featured lower CD3+ expression in the BBG compared to the TAG and MTG regions had elevated HRs ranging from 3.03 to 4.82 but did not reach statistical significance. Conclusions: Longitudinal and spatial expression patterns of both CD3+ and CD20+ suggest that increased expression in benign glands during prostate carcinogenesis is associated with an aggressive disease course. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Both humoral and cellular immunity can be significantly influenced by the immunological responses to vaccination, and both responses are essential. Vaccination is the most consistent, safe, and cost-efficient practice for controlling the COVID-19 pandemic. PATIENTS AND METHODS: Blood samples were collected from participants who received two vaccine doses of COVID-19 Pfizer/BioNTech (BNT162b2) before and on days 7 and 10 after the first and second immunization. We evaluated some hematological and immunological markers responses to the 1st and 2nd doses of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine. RESULTS: In healthy subjects' neutrophil and WBC counts significantly increased compared to those after the first dose. The results of all first-group participant categories demonstrated no discernible variations in lymphocyte counts. There was no change in IgM or IgG in all second- group cohorts, except for a considerable rise in IgG levels in people with a history of coronavirus infection following the second dosage compared to baseline. After the second dose, CD4+ T-cell and CD8+ T-cell levels rose in all groups compared to before the immunization and after the first dosage. Data demonstrated a sub-stantial rise in neutrophil-lymphocyte ratio (NLR) after the second dose of the vaccine. Individuals who had previously had COVID-19 disease experienced a considerable increase in C3 and C4 levels after the first and second dosages compared to baseline. Additionally, compared to their levels after the first dosage, C4 levels increased significantly following the second dosage. Interleukin (IL)-6, IL-15, macrophage colony-stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10/CXCL10), and macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) levels were increased after boost correlated with Spike antibody levels, supporting their utility as indicators of successful humoral immunity development in response to vaccination. CONCLUSIONS: We can conclude that the Pfizer/BioNTech vaccine produced a more potent T-cell response than humoral ones. [ABSTRACT FROM AUTHOR]

We report a case of a 54-year-old female diagnosed with HIV and antiretroviral therapy (ART) for the same. Seven years ago, she suffered from fever, cough and weight loss, was diagnosed with pulmonary tuberculosis and also seropositive for HIV. She suffered from Herpes Zoster infection, after which her ART regimen was changed to TLD (tenofovir, lamivudine and dolutegravir). The patient presented with two episodes of pyoderma gangrenosum (PG), which were biopsy-proven, corresponding to a rise in CD4 counts above 500. She responded to glucocorticoids, both systemic and topical. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary fibrosis is an irreversible condition that may be caused by known (including viral triggers such as SARS-CoV-2) and unknown insults. The latter group includes idiopathic pulmonary fibrosis (IPF), which is a chronic, progressive fibrosing interstitial pneumonia of unknown cause. The longer the insult acts on lung tissue, the lower the probability of a complete resolution of the damage. An emerging clinical entity post-COVID-19 is pulmonary fibrosis (PCPF), which shares many pathological, clinical, and immunological features with IPF. The fibrotic response in both diseases—IPF and PCPF—is orchestrated in part by the immune system. An important role regarding the inhibitory or stimulatory effects on immune responses is exerted by the immune checkpoints (ICs). The aim of the present study was to analyse the similarities and differences between CD4+, CD8+, and NK cells in the peripheral blood of patients affected by fibrotic disease, IPF, and PCPF compared with sarcoidosis patients and healthy controls. The second aim was to evaluate the expression and co-expression of PD-1 and TIGIT on CD4, CD8, and NK cells from our patient cohort. Methods: One hundred and fifteen patients affected by IPF, PCPF, and sarcoidosis at the rare pulmonary disease centre of the University of Siena were enrolled. Forty-eight patients had an IPF diagnosis, 55 had PCPF, and 12 had sarcoidosis. Further, ten healthy controls were enrolled. PCPF patients were included between 6 and 9 months following hospital discharge for COVID-19. The peripheral blood samples were collected, and through flow cytometric analysis, we analysed the expression of CD4, CD8, NK cells, PD-1, and TIGIT. Results: The results show a greater depletion of CD4 and NK cells in IPF patients compared to other groups (p = 0.003), in contrast with CD8 cells (p < 001). Correlation analysis demonstrated an indirect correlation between CD4 and CD8 cells in IPF and sarcoidosis patients (p < 0.001 = −0.87 and p = 0.042; r = −0.6, respectively). Conversely, PCPF patients revealed a direct correlation between CD4 and CD8 cells (p < 0.001; r = 0.90) accentuating an immune response restoration. The expression of PD-1 and TIGIT was abundant on T and NK cell subsets of the two lung fibrotic groups, IPF and PCPF. Analogously, the co-expression of PD-1 and TIGIT on the surfaces of CD4 and CD8 were increased in such diseases. Conclusions: Our study shines a spotlight on the immune responses involved in the development of pulmonary fibrosis, idiopathic and secondary to SARS-CoV-2 infection. We observed a significant imbalance not only in CD4, CD8, and NK blood percentages in IPF and PCPF patients but also in their functional phenotypes evaluated through the expression of ICs. [ABSTRACT FROM AUTHOR]

Rituximab has been used to treat MS patients in Iceland for over a decade. However, long-term effect of rituximab on leukocyte populations has not yet been elucidated. By retrospective analysis of flow cytometric data from 349 patients visiting the neurological ward at The National University Hospital of Iceland from 2012 to 2023 for rituximab treatment, the long-term effect of rituximab and whether the effect was dose dependent (1000mg vs 500mg) was evaluated. No difference was detected in efficacy of B cell depletion in patients treated with 500mg as an initial dose of rituximab when compared to 1000mg. Long-term use of rituximab led to an increase in T cell count (p=0,0015) in patients receiving 3-8 doses of rituximab (1.5-8 years of treatment). The increase occurred in both CD4+ (p=0,0028) and CD8+ T cells (p=0,0015) and led to a decrease in the CD4/CD8 ratio (p=0,004). The most notable difference lies in reshaping the balance between näive and effector CD8+ T cells. The clinical implications of long-term treatment with rituximab and its effect on the T cell pool needs to be explored further. Since no difference in B cell depletion was detected between the two patient groups, 1000mg as an initial dose might be excessive, suggesting a personalized dosing regimen might have therapeutic and financial advantages.