Search

Background: Older people living with HIV-1 (PLWH) experience a dual burden from the combined effects of aging and HIV-1 infection, resulting in significant immune dysfunction. Despite receiving HAART, immune reconstitution is not fully optimized. The objective of this study was to investigate the impact of aging and HAART on T cell subsets and function in PLWH across different age groups, thereby providing novel insights into the prognosis of older PLWH. Method: This study was conducted at Yunnan AIDS Care Center, China, to explore the immunological responses of old PLWH to HAART and compared with the middle-age and the younger. Blood samples were collected from 146 PLWH to analyze T cell subsets and their functions, with a particular emphasis on markers related to T cell differentiation, activation, exhaustion, inflammation, and cellular function, using multicolor flow cytometry analysis. Results: Older age may have a greater effect on long-term CD4+T cell recovery. Compared with young and middle-aged PLWH, older PLWH presented distinct alterations in their immune profile, including a decline in the Naïve CD4+T and CD8+T cell subsets, an expansion of effector memory cells, and other potential immune risk phenotypes, such as activation, exhaustion, and up-regulation of aging markers. In addition, we observed a significant association between the CD4 + EM3 subset and the CD8 + EM2 subset with HIV-1 progression, independent of age, suggesting their potential as reliable markers for assessing immune reconstitution in all PLWH. Conclusion: Our study extends previous findings showing that older participants exhibit a wide range of late differentiation, senescence, or exhaustion phenotypes in cells, including all the CD4+T and CD8+T subsets, consistent with an immunosenescent phenotype. This may accelerate poor immune recovery in older PLWH. Identifying new strategies to improve the immune risk phenotypes of older PLWH may help improve their immune reconstitution outcomes. The CD4 + EM3 subset and the CD8 + EM2 subset should be studied as additional markers of late presentation. [ABSTRACT FROM AUTHOR]

Alcohol-related cirrhosis (AC) is a condition that impacts in immunity. We analyzed changes over time in CD4+subsets in AC-patients. We included patients with alcohol use disorder admitted at least twice for treatment. Patients without evidence of liver disease were the control group (CG). We analyzed naïve, memory, TEMRA, Th1, Th2, Th17, early activated, and late activated subsets. During the follow-up, TEMRA T cells were increased (1.2 ± 1.1% vs. 2.1 ± 1.1%, p = 0.03) in AC-patients (n = 5) and Th17 cells were decreased (14.1 ± 4.3% vs. 12.3 ± 6.4%, p = 0.03) in the CG (n = 22). Late activated cells were associated with a decrease in memory cells in both the groups. This association was stronger in AC-patients (r = − 0.90, p = 0.04). The proportion of memory cells was correlated with an increased of Th1/Th2/Th17 cells in the CG (r = 0.70, r = 0.68, r = 0.63; p < 0.01, respectively), whereas in AC-patients was correlated with a decrease in Th17 cells (r = − 0.90, p = 0.03). AC-patients showed an increase in the proportion of TEMRA T cells, loss of heterogeneity and decreased CD4+ differentiation. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Dermatovenereology is the property of Xi'an Jiaotong University Periodicals Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Follicular lymphoma (FL) is an immune-responsive tumor with spontaneous remission. T cells play a pivotal role in the anti-lymphoma immune response. However, the dynamics of T cells during treatment, their impact on FL clinical outcomes, and the risk factors contributing to T-cell cytopenia remain largely unexplored. T-cell and their subsets in the peripheral blood of FL patients at diagnosis, during 2–4 cycles and after 6 cycles of treatment, as well as healthy individuals were detected by flow-cytometry. The predictive effects of T cells for early progression and risks for T-cell cytopenia were analyzed. FL patients exhibited a significant decrease in CD3+, CD4+, and CD8 + T cells compared to healthy individuals, with aging intensifying the decline of CD3+, and CD4 + T cells. Notably, a reduction in CD4 + T cells, predominantly contributing to treatment-related T-cell reduction, was only observed in patients undergoing Bendamustine-based regimens. Moreover, a significantly decreased CD4 + and CD8 + T-cell at diagnosis rather than after induction therapy was observed in patients with treatment failure. Furthermore, lower CD4 + T-cell (

Haoran Deng, Shiping Zhu, Fei Yu, Xue Song, Xinlai Jin, Xuchun Ding Department of Respiratory and Critical Care Medicine, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xuchun Ding, Email archon_01@163.comObjective: To explore the predictive value of cellular inflammatory factors and T cell subsets for disease recurrence and prognosis in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD).Methods: Serum samples were collected from the two groups to detect and compare the levels of inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], T cell subsets (CD4+, CD8+), and clinical related indicators. Pearson correlation analysis was used to analyze the correlation between inflammatory cytokines, T cell subsets, and clinical indicators. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of serum inflammatory factors and T cell subsets for acute exacerbations of COPD.Results: The observation group had higher levels of IL-1β, IL-6, TNF-α, and CD8+, and lower CD4+ levels (P< 0.05). The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) was lower, while procalcitonin (PCT) and white blood cell count (WBC) were higher (P< 0.05). Correlation analysis showed positive correlations between IL-1β, IL-6, TNF-α, and CD8+, and negative correlations with CD4+ and FEV1/FVC (P< 0.05). After 6 months, 15 out of 73 patients had acute recurrences, with higher IL-1β, IL-6, TNF-α, and CD8+ levels (P< 0.05). Binary logistic regression identified IL-1β, IL-6, TNF-α, and CD8+ as significant predictors of exacerbations, while CD4+ was protective. ROC analysis showed that combined biomarkers had the highest predictive efficiency (AUC = 0.907).Conclusion: This study is the first to integrate multiple serum inflammatory factors and T cell subsets into a comprehensive predictive model for acute recurrence of COPD within six months (AUC = 0.907), offering a more accurate prediction than traditional methods. The findings underscore the value of these biomarkers in clinical follow-up and highlight their independent predictive power, providing new insights into the interaction between immune markers and clinical indicators in COPD exacerbations.Keywords: Cellular inflammatory factors, T cell subsets, COPD, acute phase, disease recurrence, predictive value, prognosis

Introduction: Platelets are hyperactived during acute COVID-19, promoting clotting and modulating immune-cell responses. Immune thrombocytopenia in adults can manifest as an uncommon complication resulting from various viral infections or as a rare adverse event associated with vaccination. However, their role in convalescent COVID-19 patients remains underexplored. This study examines platelet dynamics early in the pandemic, 48 days post-symptom onset, in unvaccinated patients. Methods: This longitudinal study included 298 unvaccinated COVID-19 patients (17 mild, 281 moderate) from multiple centers. Clinical evaluations and peripheral lymphocyte subset analyses via flow cytometry were conducted upon admission and on day 48 post-symptom onset (DPSO 48). Results: At DPSO 48, 5.3% of moderate COVID-19 patients exhibited high platelet counts (>300×109/L), associated with elevated total T-cells (26.4%), CD4 T-cells (24.4%), CD8 T-cells (36.9%), and Tregs (33.9%) compared to patients with normal platelet counts. However, the CD4/CD8 T-cell ratio and T-cell subset frequencies remained unaffected, indicating ongoing T-cell homeostasis restoration. Additionally, a significant positive correlation (r=0.636, p=0.03) was found between platelet counts and B cells in patients with elevated platelet counts. Discussion: Platelets may play a pivotal role in immune regulation during the recovery phase of COVID-19. Targeting platelets and their secreted mediators could improve immune balance in patients with immune disorders, highlighting a potential therapeutic approach for enhancing recovery in post-COVID-19 patients. [ABSTRACT FROM AUTHOR]

Intra-articular ankle fracture (IAF) often leads to post-traumatic osteoarthritis (PTOA), resulting in significant long-term morbidity. While previous research has focused on the inflammatory cytokines and matrix metalloproteinases within the synovial fluid fracture hematoma (SFFH), the immune cell populations within SFFH that contribute to PTOA development remain underexplored. This study aimed to characterize the immune cell populations in SFFH to better understand their role in the inflammatory response and potential for inducing lasting cartilage damage. Twenty-four patients with IAF underwent surgical ankle aspiration to collect SFFH, which was analyzed using polychromatic flow cytometry. The analysis revealed that 72.8% of the CD45+ cells were lymphocytes, predominantly CD3+ T cells (76.5%), with 42.1% being CD4+ and 39.2% CD8+ T cells. Additionally, monocytes accounted for 21.2% of CD45+ cells, with small populations of natural killer cells and myeloid-derived suppressor cells also present. These findings emphasize the predominance of T cells, particularly CD4+ subsets, in the immune response following IAF. Understanding these dynamics is essential for developing targeted interventions to prevent PTOA. Future research should focus on elucidating the specific roles of these immune cell populations in PTOA progression and exploring potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer‐related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non‐small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min‐max) = 64.03 (45–83); 20 stage I–III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD‐1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD‐1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is a significant challenge in the field of cardiovascular diseases. Inflammation, myocardial fibrosis, and coronary microcirculation dysfunction are the core pathophysiological mechanisms of HFpEF. As a key part of adaptive immune response, T cell subsets widely participate in the above process through various mechanisms, further aggravating the damage of myocardial structure and function, and ultimately leading to the development of HFpEF. This article provides a comprehensive review on the roles of immunity and inflammation in HFpEF, summarizes the characteristics and functions of different T cell subsets involved in HFpEF, and aims to explore novel biomarkers and potential therapeutic targets by targeting T cell subsets. [ABSTRACT FROM AUTHOR]

Objectives: Inflammasomes are associated with various autoimmune diseases. Herein, we aimed to study the occurrence of inflammasomes in peripheral blood mononuclear cells (PBMCs) from patients with autoimmune thyroiditis (AIT), and the relationship between their abundance and the inflammatory response index of AIT. Furthermore, we examined the effect of iodine on inflammasomes containing NLR family pyrin domain-containing 3 (NLRP3) and inflammasome activation of helper T (Th) cell differentiation regulation in cultured PBMCs. Methods: We collected PBMCs and serum samples from 50 patients with AIT with normal thyroid function and 50 controls matched for age and sex. In PBMCs, the mRNA and protein expressions of certain inflammasome constituents (e.g., NLRP1, NLRP3, absent in melanoma 2 (AIM2) and caspase-1), interleukin (IL)-1β and IL-18 were assessed using qRT-PCR and western blotting. Enzyme-linked immunosorbent assays (ELISAs) assessed the serum levels of IL-1β and IL-18. Flow cytometry was employed to examine NLRP3 expression on CD14+ monocytes and Th1 and Th17 cell percentages in the groups. AIT- or healthy control-derived PBMCs were stimulated using sodium iodide, with or without lipopolysaccharide (LPS) for 72 h. Results: PBMCs from patients with AIT had significantly higher levels of pro-IL-18, pro-IL-1β and NLRP3 than did the PBMCs from the healthy controls (P < 0.05). Compared with those from the controls, AIT-derived PBMCs had enhanced levels of active IL-18 and active caspase-1 p20 (P < 0.05), whereas their abundance of active IL-1β was similar (P > 0.05). In serum, the AIT group had enhanced levels of IL-18 compared with the healthy controls (P < 0.05) but had similar levels of IL-1β (P > 0.05). NLRP3 expression on CD14+ monocytes from AIT patients was significantly augmented compared with the healthy controls (P< 0.01). Significantly increased percentages of Th1 and Th17 cells were detected in AIT patients compared with those in the healthy participants (P < 0.001). Sodium iodide treatment upregulated NLRP3 expression in PBMCs during 72 h of culture (P < 0.001). The percentage of Th1 and Th17 cells in AIT patients increased in an iodine-dependent manner (P < 0.01). Iodine had no significant effect on the number of these cells in the healthy control group (P > 0.05). Conclusion: AIT-derived PBMC NLRP3 activity and expression increased. Iodine might regulate the immune and inflammatory response of patients with AIT by activating NLRP3 and promoting Th1 and Th17 cell differentiation.

Abstract Objectives Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients. Various mechanisms have been implicated in the pathogenesis of DR. Previous studies have observed the relationship between immune factors and DR, but the causal relationship has not been determined. Methods We conducted a two-sample Mendelian randomization (MR) analysis of 731 immune cells and DR, using publicly available genome-wide association study (GWAS) summary statistics, to evaluate potential causal relationships between them. Four types of immune traits were included in the analysis through flow cytometry. GWAS statistics for DR were obtained from the Finngen database, which performed GWAS on 190,594 European individuals (Ncase = 14,584, Ncontrol = 176,010) to assess genetically predicted DR. The primary method used to perform causality analysis was inverse variance weighting (IVW). Results Following false discovery rate (FDR) correction, 11MFI-DR, 5AC-DR, 5RC-DR, and 1MP-DR reached a significant causal association level (PFDR < 0.05). Notably, all AC traits exhibited potential associations with a decreased risk of DR(OR 1). The highest proportion of T-cell subsets in the final results. Conclusion This study elucidates that the progression of DR is intricately influenced by immune responses, thereby confirming the immunological susceptibility of DR. Our findings may offer new targets for diagnosing and treating DR, as well as aid in developing therapeutic strategies from an immunological standpoint.

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10−15) and LAG3 (rs67706382, p = 6.16× 10−16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of Yangzheng Touxie Qudu method combined with NAC regimen (docetaxel + epirubicin + cyclophosphamide) chemotherapy on efficacy, T cell subsets and cancer-related fatigue in patients with triple negative breast cancer. METHODS: From Jun. 2022 to Jun. 2023, totally 100 cases of triple negative breast cancer diagnosed and treated in the hospital were extracted to be divided into the control group and observation group according to the random number table method, with 50 cases in each group. The control group was treated with NAC regimen, while the observation group received self formulated Yangzheng Touxie Qudu formula combined with NAC regimen. The efficacy, T-lymphocyte subsets, inflammatory factors, cancer-related fatigue levels, and incidence of adverse drug reactions of two groups were observed. RESULTS: The total effective rate of observation group was 82. 00% (41/50), significantly higher than that 58. 00% (29/50) of control group, the difference was statistically significant (P < 0. 05). Compared with before treatment, CD3+, CD4+, CD4+ / CD8+, interleukin (IL)-12 and IL-2 levels increased significantly in both groups after treatment, and the observation group was higher than the control group; compared with before treatment, CD8+, tumor necrosis factor-α, soluble interleukin-2 receptor levels, physical, cognitive and emotional fatigue scores decreased in both groups after treatment, and the observation group was lower than the control group, with statistically significant differences (P <0.05). The incidence of adverse drug reactions in observation group and control group was respectively 24.00% (12/50) and 28.00% (14/50), with no statistically significant difference (P>0.05). CONCLUSIONS: Yangzheng Touxie Qudu method combined with NAC regimen in the treatment of patients with triple negative breast cancer can significantly improve the efficacy and T cell subsets levels, reduce inflammatory reactions, and improve cancer-related fatigue with higher safety. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV‐specific T cells, which is regulated by various co‐suppressor molecules. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) is among these co‐suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV‐specific T cells. CTLA‐4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA‐4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA‐4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA‐4 may contribute to HBV infection, as well as the development of HBV‐induced cirrhosis and hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Many research laboratories have long-term repositories of cryopreserved peripheral blood mononuclear cells (PBMC), which are costly to maintain but are of uncertain utility for immunological studies after decades in storage. This study investigated preservation of cell surface phenotypes and invitro functional capacity of PBMC from viraemic HIV+ patients and healthy seronegative control subjects, after more than 20 years of cryopreservation. Methods: PBMC were assessed by 18-colour flow cytometry for major lymphocyte subsets within T, B, NK, and dendritic cells and monocytes. Markers of T-cell differentiation and activation were compared with original immunophenotyping performed in 1995/1996 on fresh blood at the time of collection. Functionality of PBMC was assessed by culture with influenza antigen or polyclonal T-cell activation, to measure upregulation of activation-induced CD25 and CD134 (OX40) on CD4 T cells and cytokine production at day 2, and proliferative CD25+ CD4 blasts at day 7. RNA was extracted from cultures containing proliferating CD4+ blast cells, and intracellular HIV RNA was measured using short amplicons for both the Double R and pol region pi code assays, whereas long 4-kbp amplicons were sequenced. Results: All major lymphocyte and T-cell subpopulations were conserved after long-term cryostorage, except for decreased proportions of activated CD38+HLA-DR+ CD4 and CD8 T cells in PBMC from HIV+ patients. Otherwise, differences in T-cell subpopulations between recent and long-term cryopreserved PBMC primarily reflected donor age-associated or HIV infectionassociated effects on phenotypes. Proportions of naïve, memory, and effector subsets of T cells from thawed PBMC correlated with results from the original flow cytometric analysis of respective fresh blood samples. Antigen-specific and polyclonal T-cell responses were readily detected in cryopreserved PBMC from HIV+ patients and healthy control donors. Intracellular HIV RNA quantitation by pi code assay correlated with original plasma viral RNA load results. Full-length intracellular and supernatant-derived amplicons were generated from 5/12 donors, and sequences were ≥80% wild-type, consistent with replication competence. Conclusions: This unique study provides strong rationale and validity for using well-maintained biorepositories to support immunovirological research even decades after collection. [ABSTRACT FROM AUTHOR]

Objectives: Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients. Various mechanisms have been implicated in the pathogenesis of DR. Previous studies have observed the relationship between immune factors and DR, but the causal relationship has not been determined. Methods: We conducted a two-sample Mendelian randomization (MR) analysis of 731 immune cells and DR, using publicly available genome-wide association study (GWAS) summary statistics, to evaluate potential causal relationships between them. Four types of immune traits were included in the analysis through flow cytometry. GWAS statistics for DR were obtained from the Finngen database, which performed GWAS on 190,594 European individuals (Ncase = 14,584, Ncontrol = 176,010) to assess genetically predicted DR. The primary method used to perform causality analysis was inverse variance weighting (IVW). Results: Following false discovery rate (FDR) correction, 11MFI-DR, 5AC-DR, 5RC-DR, and 1MP-DR reached a significant causal association level (PFDR < 0.05). Notably, all AC traits exhibited potential associations with a decreased risk of DR(OR < 1), while a majority of MFI traits, along with the singular MP trait, exhibited potential associations with an increased risk of DR (OR > 1). The highest proportion of T-cell subsets in the final results. Conclusion: This study elucidates that the progression of DR is intricately influenced by immune responses, thereby confirming the immunological susceptibility of DR. Our findings may offer new targets for diagnosing and treating DR, as well as aid in developing therapeutic strategies from an immunological standpoint. [ABSTRACT FROM AUTHOR]

Objective: To reveal effect of celastrol （Cel） on apoptosis of liver and kidney cells in preeclampsia （PE） rats and its protective effect. Methods: Fifty pregnant SD rats were randomly divided into 5 groups（ n=10）: Control group, PE group, PE+lowdose Cel group （PE+L-Cel）, PE+medium-dose Cel group （PE+M-Cel）, PE+high-dose Cel group （PE+H-Cel）, PE rat model was induced by injection of lipopolysaccharide through tail vein. Rats in PE+L-Cel group, PE+M-Cel group and PE+H-Cel group were intraperitoneally injected with 5, 10 and 20 mg（/kg·d） Cel daily from 14~20 day of pregnancy. Control group and PE group were injected with equal volume of normal saline. Systolic blood pressure （SBP） and urine albumin of rats in each group were measured after treatment. Cell apoptosis of liver and kidney tissues were detected by TUNEL staining. Bcl-2 and Caspase-9 expressions in liver and kidney tissues were detected by immunohistochemical staining. ELISA was used to detect serum IFN-γ, IL-4, IL-17 and IL-10 levels. Results: Compared with PE group, SBP and urine albumin levels of PE+L-Cel group, PE+M-Cel group and PE+H-Cel group were decreased （P<0.05）, cells apoptosis rates of liver and kidney tissues were decreased （P<0.05）, positive expression of Caspase-9 was significantly reduced, Bcl-2 level was significantly increased, serum IFN-γ and IL-17 levels were reduced （P<0.05）, while IL-4 and IL-10 levels were increased （P<0.05）. Conclusion: Cel can reduce symptoms of PE rats and inhibit liver and kidney cell apoptosis, which may play a therapeutic effect by correcting imbalance of Th1/Th2 and Th17/Treg cells in PE rats. [ABSTRACT FROM AUTHOR]

IntroductionPlatelets are hyperactived during acute COVID-19, promoting clotting and modulating immune-cell responses. Immune thrombocytopenia in adults can manifest as an uncommon complication resulting from various viral infections or as a rare adverse event associated with vaccination. However, their role in convalescent COVID-19 patients remains underexplored. This study examines platelet dynamics early in the pandemic, 48 days post-symptom onset, in unvaccinated patients.MethodsThis longitudinal study included 298 unvaccinated COVID-19 patients (17 mild, 281 moderate) from multiple centers. Clinical evaluations and peripheral lymphocyte subset analyses via flow cytometry were conducted upon admission and on day 48 post-symptom onset (DPSO 48).ResultsAt DPSO 48, 5.3% of moderate COVID-19 patients exhibited high platelet counts (>300×109/L), associated with elevated total T-cells (26.4%), CD4 T-cells (24.4%), CD8 T-cells (36.9%), and Tregs (33.9%) compared to patients with normal platelet counts. However, the CD4/CD8 T-cell ratio and T-cell subset frequencies remained unaffected, indicating ongoing T-cell homeostasis restoration. Additionally, a significant positive correlation (r=0.636, p=0.03) was found between platelet counts and B cells in patients with elevated platelet counts.DiscussionPlatelets may play a pivotal role in immune regulation during the recovery phase of COVID-19. Targeting platelets and their secreted mediators could improve immune balance in patients with immune disorders, highlighting a potential therapeutic approach for enhancing recovery in post-COVID-19 patients.

Objective: To investigate the relationship between serum osteopontin (OPN), high mobility group protein B1 (HMGB1) and T cell subsets and chemotherapy efficacy in patients with multidrug-resistant pulmonary tuberculosis (MDR-TB). Methods: 147 MDR-TB patients (MDR-TB group) admitted to Xuzhou Infectious Disease Hospital from March 2018 to September 2021 were selected, and 109 non-MDR-TB patients (control group) admitted to Xuzhou Infectious Disease Hospital during the same period were selected. The correlation between serum OPN, HMGB1 and peripheral blood T cell subsets in MDR-TB group was analyzed by Pearson correlation analysis. The factors of unsuccessful MDR-TB treatment were analyzed by multivariate Logistic regression analysis. Results: Serum OPN and HMGB1 in MDR-TB group were positively correlated with peripheral blood CD8+ count (P<0.05), and negatively correlated with peripheral blood CD3+ count, CD4+ count and CD4+ /CD8+ ratio (P<0.05). Multivariate Logistic regression analysis showed that cavity, high OPN and high HMGB1 were risk factors for unsuccessful MDR-TB treatment (P<0.05). Conclusion: The levels of serum OPN and HMGB1 in MDR-TB patients are significantly increase, which are relate to the abnormality of T cell subsets and the failure of chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of salmeterol fluticasone combined with budesonide inhalation aerosol on bronchial asthma and Treg T cell subsets. Methods: Eighty patients with bronchial asthma admitted from June 2021 to April 2023 were selected and divided into observation group and matched group, 40 each. The matched group was treated with salmeterol fluticasone inhalation, and the observation group was treated with salmeterol fluticasone combined with budesonide inhalation aerosol inhalation. The signs and symptoms disappeared time, tumor necrosis factor pretherapy and 1 month post-treatment were compared between the two groups (tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), The expression levels of interleukin-6 (IL-6) and T cell subsets were detected, and the incidence of adverse reactions was compared between the two groups. Results: In the observation group, the disappearance time of wet rales and cough were shorter than that of the matched group (P<0.05); pretherapy, There was no difference in TNF-α, IFN-γ, and IL-6 levels between the two groups (P>0.05), Both were decreased after the treatment, And, when compared with the matched group, The value was lower in the observation group(P<0.05); There was no difference in CD4+, CD3+ and CD4+/CD8+ values between the two previous treatment groups (P>0.05), CD4+, CD3+, and CD4+/CD8+ values were increased in the post / treatment observation group, And the observation group was higher than the matched group (P<0.05); There was no difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: The application effect of salmeterol fluticasone combined with budesonide inhalation aerosol in the treatment of bronchial asthma is significant, which can shorten the duration of symptoms and signs of patients, reduce the reaction of inflammatory factors, and improve the ratio of T cell subsets, with high safety. [ABSTRACT FROM AUTHOR]

Introduction: The gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis. Methods: According to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines. Results: We showed the presence of 26 identifiable differential microbiomes in the gut and 44 metabolic pathways between healthy controls and the different time points in the development of TB in patients. Five bacterial genera (Bacteroides, Bifidobacterium, Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4/CD8, whereas three bacterial taxa (Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4. Three bacterial taxa (Faecalibacterium, Ruminococcus, and Dorea) were most closely associated with IL-4. Ruminococcus was most closely associated with IL-2 and IL-10. Conclusion: Diverse microorganisms, subsets of T cells, and cytokines, exhibiting varying relative abundances and structural compositions, were observed in both healthy controls and patients throughout distinct phases of tuberculosis. Gaining insight into the function of the gut microbiome, T cell subsets, and cytokines may help modulate therapeutic strategies for TB. [ABSTRACT FROM AUTHOR]

BackgroundMany research laboratories have long-term repositories of cryopreserved peripheral blood mononuclear cells (PBMC), which are costly to maintain but are of uncertain utility for immunological studies after decades in storage. This study investigated preservation of cell surface phenotypes and in-vitro functional capacity of PBMC from viraemic HIV+ patients and healthy seronegative control subjects, after more than 20 years of cryopreservation.MethodsPBMC were assessed by 18-colour flow cytometry for major lymphocyte subsets within T, B, NK, and dendritic cells and monocytes. Markers of T-cell differentiation and activation were compared with original immunophenotyping performed in 1995/1996 on fresh blood at the time of collection. Functionality of PBMC was assessed by culture with influenza antigen or polyclonal T-cell activation, to measure upregulation of activation-induced CD25 and CD134 (OX40) on CD4 T cells and cytokine production at day 2, and proliferative CD25+ CD4 blasts at day 7. RNA was extracted from cultures containing proliferating CD4+ blast cells, and intracellular HIV RNA was measured using short amplicons for both the Double R and pol region pi code assays, whereas long 4-kbp amplicons were sequenced.ResultsAll major lymphocyte and T-cell subpopulations were conserved after long-term cryostorage, except for decreased proportions of activated CD38+HLA-DR+ CD4 and CD8 T cells in PBMC from HIV+ patients. Otherwise, differences in T-cell subpopulations between recent and long-term cryopreserved PBMC primarily reflected donor age-associated or HIV infection-associated effects on phenotypes. Proportions of naïve, memory, and effector subsets of T cells from thawed PBMC correlated with results from the original flow cytometric analysis of respective fresh blood samples. Antigen-specific and polyclonal T-cell responses were readily detected in cryopreserved PBMC from HIV+ patients and healthy control donors. Intracellular HIV RNA quantitation by pi code assay correlated with original plasma viral RNA load results. Full-length intracellular and supernatant-derived amplicons were generated from 5/12 donors, and sequences were ≥80% wild-type, consistent with replication competence.ConclusionsThis unique study provides strong rationale and validity for using well-maintained biorepositories to support immunovirological research even decades after collection.

Objective: Low molecular mass protein 7 (LMP7) aggravates abnormal T cell differentiation and atherosclerosis, but its clinical role in acute ischemic stroke (AIS) is still unclear. This study aimed to investigate the correlation of peripheral blood mononuclear cell (PBMC) LMP7 with T cell subsets, disease severity, and prognosis in AIS patients. Methods: A total of 162 AIS patients were enrolled for detecting PBMC LMP7 and T helper (Th) 1, Th2, and Th17 cells via reverse transcriptase-polymerase chain reaction and flow cytometry, respectively. In addition, PBMC LMP7 at discharge was also quantified. Results: Increased LMP7 at admission was associated with decreased Th2 cells (P=0.014), elevated Th17 cells (P<0.001), C-reactive protein (P=0.005), National Institutes of Health Stroke Scale (NIHSS) score (P=0.007), and disease severity (defined by NIHSS score) (P=0.010). LMP7 at admission reflected a high risk of stroke recurrence (area under curve (AUC): 0.748, 95% confidence interval (CI): 0.564-0.932), but not mRS score at month 3 (M3) >2 (AUC: 0.585, 95%CI: 0.479-0.691), or death (AUC: 0.723, 95%CI: 0.338-1.000). LMP7 at discharge was reduced compared to that at admission (P<0.001). LMP7 at discharge was positively correlated with the risk of stroke recurrence (AUC: 0.849, 95%CI: 0.735-0.963) and death (AUC: 0.919, 95%CI: 0.836-1.000), but had a weak capacity to reflect mRS score at M3 >2 (AUC: 0.671, 95%CI: 0.578-0.765). Conclusion: PBMC LMP7 positively correlates with Th17 cells, inflammation, and disease severity in AIS patients, meanwhile, its level at discharge shows a good ability to reflect the risks of stroke recurrence and death. [ABSTRACT FROM AUTHOR]

[Objectives]This study aimed to investigate the effect of Armadillo/β-catenin like repeat containing protein(EmARM-β), a Th1 cytokine stimulatory molecule from Eimeria maxima on functions of chicken immune-related cells. [Methods]In this study, chicken peripheral blood mononuclear cell(PBMC), CD8+T cells, and CD4+CD25-T cells were isolated by density gradient cell centrifugation method and immunomagnetic bead sorting method, respectively. Subsequently, EmARM-β recombinant protein(rEmARM-β)was incubated with the above cells in vitro, CCK-8 solution and qPCR were used to detect and analyze the effects on the proliferation ability of the above cells and the secretion levels of cytokines, respectively. [Results]The results showed that purity of chicken CD8+T cells and CD4+CD25-T cells were 93.01% and 88.88%, respectively. rEmARM-β significantly enhanced the proliferation capacity, upregulated Th1 type cytokines(ifn-γ, and il-2)and proinflammatory cytokines(il-1β, il-6, and il-17a)mRNA levels in chicken PBMC compared with the control group. Effective stimulations of rEmARM-β on the cell proliferation capacity and mRNA levels of ifn-γ, il-2, tnf-α, perforin, fasl, and fas in chicken CD8+T cells were also observed. The molecule significantly promoted cell proliferation capacity, upregulated the mRNA levels of ifn-γ and il-2, and downregulated the mRNA levels of il-4 and il-10 in chicken CD4+CD25-T cells. [Conclusions]EmARM-β, the Th1 cytokine stimulatory molecule, could effectively promote cell proliferation, secretions of Th1 cytokines and proinflammatory cytokines of chicken PBMC and T cell subsets, suggesting the EmARM-β is the potential candidate antigen to develop novel vaccine against chicken coccidiosis. [ABSTRACT FROM AUTHOR]

People who use drugs (PWUD) are at a high risk of contracting and developing severe coronavirus disease 2019 (COVID-19) and other infectious diseases due to their lifestyle, comorbidities, and the detrimental effects of opioids on cellular immunity. However, there is limited research on vaccine responses in PWUD, particularly regarding the role that T cells play in the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we show that before vaccination, PWUD did not exhibit an increased frequency of preexisting cross-reactive T cells to SARS-CoV-2 and that, despite the inhibitory effects that opioids have on T-cell immunity, standard vaccination can elicit robust polyfunctional CD4+ and CD8+ T-cell responses that were similar to those found in controls. Our findings indicate that vaccination stimulates an effective immune response in PWUD and highlight targeted vaccination as an essential public health instrument for the control of COVID-19 and other infectious diseases in this group of high-risk patients.

γδ T cells, a specialized subset of T lymphocytes, have garnered significant attention within the realm of cancer immunotherapy. Operating at the nexus between adaptive and innate immunological paradigms, these cells showcase a profound tumor discernment repertoire, hinting at novel immunotherapeutic strategies. Significantly, these cells possess the capability to directly identify and eliminate tumor cells without reliance on HLA-antigen presentation. Furthermore, γδ T cells have the faculty to present tumor antigens to αβ T cells, amplifying their anti-tumoral efficacy.Within the diverse and heterogeneous subpopulations of γδ T cells, distinct immune functionalities emerge, manifesting either anti-tumor or pro-tumor roles within the tumor microenvironment. Grasping and strategically harnessing these heterogeneous γδ T cell cohorts is pivotal to their integration in tumor-specific immunotherapeutic modalities. The aim of this review is to describe the heterogeneity of the γδ T cell lineage and the functional plasticity it generates in the treatment of malignant tumors. This review endeavors to elucidate the intricate heterogeneity inherent to the γδ T cell lineage, the consequential functional dynamics in combating malignancies, the latest advancements from clinical trials, and the evolving landscape of γδ T cell-based oncological interventions, while addressing the challenges impeding the field. [ABSTRACT FROM AUTHOR]

Background: Patients with immunodeficiencies commonly experience diagnostic delays resulting in morbidity. There is an unmet need to identify patients earlier, especially those with high risk for complications. Compared to immunoglobulin quantification and flowcytometric B cell subset analysis, expanded T cell subset analysis is rarely performed in the initial evaluation of patients with suspected immunodeficiency. The simultaneous interpretation of multiple immune variables, including lymphocyte subsets, is challenging. Objective: To evaluate the diagnostic value of cluster analyses of immune variables in patients with suspected immunodeficiency. Methods: Retrospective analysis of 38 immune system variables, including seven B cell and sixteen T cell subpopulations, in 107 adult patients (73 with immunodeficiency, 34 without) evaluated at a tertiary outpatient immunology clinic. Correlation analyses of individual variables, k‐means cluster analysis with evaluation of the classification into "no immunodeficiency" versus "immunodeficiency" and visual analyses of hierarchical heatmaps were performed. Results: Binary classification of patients into groups with and without immunodeficiency was correct in 54% of cases with the full data set and increased to 69% and 75% of cases, respectively, when only 16 variables with moderate (p <.05) or 7 variables with strong evidence (p <.01) for a difference between groups were included. In a cluster heatmap with all patients but only moderately differing variables and a heatmap with only immunodeficient patients restricted to T cell variables alone, segregation of most patients with common variable immunodeficiency and combined immunodeficiency was observed. Conclusion: Cluster analyses of immune variables, including detailed lymphocyte flowcytometry with T cell subpopulations, may support clinical decision making for suspected immunodeficiency in daily practice. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) has cancer-like pathophysiology. In this study, we aimed to investigate the phenotype of peripheral blood (PB) T cell subsets and immune checkpoint inhibitor expression of ADPKD patients across different chronic kidney disease (CKD) stages. Seventy-two patients with ADPKD and twenty-three healthy controls were included in the study. The patients were grouped into five different CKD stages, according to glomerular filtration rate (GFR). PB mononuclear cells were isolated and T cell subsets and cytokine production were examined by flow cytometry. CRP levels, height-adjusted total kidney volume (htTKV), rate of hypertension (HT) differed significantly across different GFR stages in ADPKD. T cell phenotyping revealed significantly elevated CD3+ T cells, CD4+, CD8+, double-negative, and double-positive subsets and significantly elevated IFN-γ and TNF-α producing subsets of CD4+, CD8+ cells. The expression of checkpoint inhibitors CTLA-4, PD-1, and TIGIT by T cell subsets was also increased to various extent. Additionally, Treg cell numbers and suppressive markers CTLA-4, PD-1, and TIGIT were significantly elevated in ADPKD patients' PB. Treg CTLA4 expression and CD4CD8DP T cell frequency in patients with HT were significantly higher. Lastly, HT and increased htTKV and higher frequency of PD1+ CD8SP were found to be risk factors for rapid disease progression. Our data provide the first detailed analyses of checkpoint inhibitor expression by PB T cell subsets during stages of ADPKD, and that a higher frequency of PD1+ CD8SP cells is associated with rapid disease progression. [ABSTRACT FROM AUTHOR]

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in primary Sjögren's syndrome (pSS). The aim of this research was to assess the imbalance of circulating CD8+ T cell subsets. We analyzed blood samples from 34 pSS patients and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages, using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA and CD45. For immunophenotyping of 'polarized' CD8+ T cell subsets, we used the following monoclonal antibodies: CXCR5, CCR6, CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, rheumatoid factor, the Schirmer test and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS. [ABSTRACT FROM AUTHOR]

Abstract Background Selective IgA deficiency (SIgAD) is the most prevalent inborn errors of immunity with almost unknown etiology. This study aimed to investigate the clinical diagnostic and prognostic values of lymphocyte subsets and function in symptomatic SIgAD patients. Methods A total of 30 available SIgAD patients from the Iranian registry and 30 age-sex-matched healthy controls were included in the present study. We analyzed B and T cell peripheral subsets and T cell proliferation assay by flow cytometry in SIgAD patients with mild and severe clinical phenotypes. Results Our results indicated a significant increase in naïve and transitional B cells and a strong decrease in marginal zone-like and switched memory B-cells in SIgAD patients. We found that naïve and central memory CD4+ T cell subsets, as well as Th1, Th2 and regulatory T cells, have significantly decreased. On the other hand, there was a significant reduction in central and effector memory CD8+ T cell subsets, whereas proportions of both (CD4+ and CD8+) terminally differentiated effector memory T cells (TEMRA) were significantly elevated in our patients. Although some T cell subsets in severe SIgAD were similar, a decrease in marginal-zone and switched memory B cells and an increase in CD21low B cell of severe SIgAD patients were slightly prominent. Moreover, the proliferation activity of CD4+ T cells was strongly impaired in SIgAD patients with a severe phenotype. Conclusion SIgAD patients have varied cellular and humoral deficiencies. Therefore, T cell and B cell assessment might help in better understanding the heterogeneous pathogenesis and prognosis estimation of the disease.

As previously reported, inflammatory activity initiated by intradermal injection of multiple growing feather (GF)-pulps of a chicken with lipopolysaccharide, and the subsequent periodic sampling of GFs and blood, enables the longitudinal evaluation of in vivo tissue- and systemic-inflammatory activities by ex vivo laboratory analyses. To demonstrate the suitability of this two-window approach to monitor and assess vaccine responses, two groups of chickens were immunized by intramuscular injection of mouse IgG (mIgG), mIgG in alum adjuvant (Alum&mIgG), or PBS-vehicle (Group I and II at 7- and 7- and 11-weeks, respectively). Plasma levels of mIgG-specific antibodies were monitored by ELISA for 28 days post-primary- and secondary-immunizations. To examine the cellular responses, 20 GF-pulps per bird were injected with mIgG on Day-10 or Day-5 post-primary- or -secondary-immunization, respectively. Two GFs were collected before- and at various times (0.25 to 7 days) post-injection for leukocyte population- and cytokine mRNA expression-analyses. The observed primary- and secondary-antibody response profiles were as expected for a T-dependent antigen. Leukocyte- and cytokine-profiles established in GF-pulps revealed temporal, qualitative, and quantitative differences in local naïve, primary, and secondary leukocyte-effector responses to antigen. This study demonstrates the unique opportunity in the avian model to monitor both cell- and antibody-mediated immune responses using minimally invasive techniques.

γδ T cells, a specialized subset of T lymphocytes, have garnered significant attention within the realm of cancer immunotherapy. Operating at the nexus between adaptive and innate immunological paradigms, these cells showcase a profound tumor discernment repertoire, hinting at novel immunotherapeutic strategies. Significantly, these cells possess the capability to directly identify and eliminate tumor cells without reliance on HLA-antigen presentation. Furthermore, γδ T cells have the faculty to present tumor antigens to αβ T cells, amplifying their anti-tumoral efficacy.Within the diverse and heterogeneous subpopulations of γδ T cells, distinct immune functionalities emerge, manifesting either anti-tumor or pro-tumor roles within the tumor microenvironment. Grasping and strategically harnessing these heterogeneous γδ T cell cohorts is pivotal to their integration in tumor-specific immunotherapeutic modalities. The aim of this review is to describe the heterogeneity of the γδ T cell lineage and the functional plasticity it generates in the treatment of malignant tumors. This review endeavors to elucidate the intricate heterogeneity inherent to the γδ T cell lineage, the consequential functional dynamics in combating malignancies, the latest advancements from clinical trials, and the evolving landscape of γδ T cell-based oncological interventions, while addressing the challenges impeding the field.

Objective: To evaluate the clinical efficacy of TCM Buwu decoction combined with phototherapy in the treatment of advanced vitiligo, and to detect the changes of heme oxygenase-1（ HO-1） level, T cell subpopulation, nuclear factor E2-related transcription factor 2（Nrf2） and dead bone tablet 1（p62） mRNA in peripheral blood of patients before and after treatment, so as to explore the preliminary mechanism of action. Methods: According to the inclusion criteria of advanced vitiligo patients, sixty patients were selected and randomly divided into obesevation group （30 cases） and control group（30 cases）. Both groups were treated with 308 excimer light, and the observation group was treated with Buwu decoction on the basis of phototherapy. The clinical efficacy of the two groups was evaluated, and the level of HO-1 in serum was detected by ELISA; T cell subsets of peripheral blood lymphocytes were detected by flow cytometry; the expressions of Nrf2 and p62 mRNA in PBMC were detected by RT-qPCR. Results: There was significant difference in clinical efficacy between the two groups（ Z=0.019, P<0.05）. The level of HO-1 in peripheral blood of 2 groups after treatment was significantly higher than that before treatment （P<0.01）. After treatment, the proportion of peripheral blood lymphocytes CD3+CD8+T cells was lower than before treatment, and the proportion of CD4+/CD8+ was significantly higher than before treatment （P< 0.01）. The relative expression levels of Nrf2 and p62 mRNA in peripheral blood lymphocytes of two groups were higher after treatment than before treatment （P<0.01）. Conclusion: TCM combined with 308 excimer light can effectively treat advanced vitiligo, and can up-regulate Nrf2 and p62 mRNA to promote the expression of HO-1 in its downstream, thus playing antioxidant, anti-inflammatory and immune regulation roles, and reduce the proportion of CD3+CD8+T cells in peripheral blood, whose effect is better than that of simple light therapy group. [ABSTRACT FROM AUTHOR]

Patient-derived autologous chimeric antigen receptor (CAR)-T cell therapy is a revolutionary breakthrough in immunotherapy and has made impressive progress in both preclinical and clinical studies. However, autologous CAR-T cells still have notable drawbacks in clinical manufacture, such as long production time, variable cell potency and possible manufacturing failures. Allogeneic CAR-T cell therapy is significantly superior to autologous CAR-T cell therapy in these aspects. The use of allogeneic CAR-T cell therapy may provide simplified manufacturing process and allow the creation of ‘off-theshelf’ products, facilitating the treatments of various types of tumors at less delivery time. Nevertheless, severe graft-versus-host disease (GvHD) or hostmediated allorejection may occur in the allogeneic setting, implying that addressing these two critical issues is urgent for the clinical application of allogeneic CAR-T cell therapy. In this review, we summarize the current approaches to overcome GvHD and host rejection, which empower allogeneic CAR-T cell therapy with a broader future. [ABSTRACT FROM AUTHOR]

The thymus gland is a central lymphoid organ in which developing T cell precursors, known as thymocytes, undergo differentiation into distinct type of mature T cells, ultimately migrating to the periphery where they exert specialized effector functions and orchestrate the immune responses against tumor cells, pathogens and selfantigens. The mechanisms supporting intrathymic T cell differentiation are pleiotropically regulated by thymic peptide hormones and cytokines produced by stromal cells in the thymic microenvironment and developing thymocytes. Interestingly, in the same way as T cells, thymic hormones (herein exemplified by thymosin, thymulin and thymopoietin), can circulate to impact immune cells and other cellular components in the periphery. Evidence on how thymic function influences tumor cell biology and response of patients with cancer to therapies remains unsatisfactory, although there has been some improvement in the knowledge provided by recent studies. Herein, we summarize research progression in the field of thymus-mediated immunoendocrine control of cancer, providing insights into how manipulation of the thymic microenvironment can influence treatment outcomes, including clinical responses and adverse effects of therapies. We review data obtained from clinical and preclinical cancer research to evidence the complexity of immunoendocrine interactions underpinning anti-tumor immunity. [ABSTRACT FROM AUTHOR]

To investigate the clinical efficacy of dexamethasone (Dex) combined with isoniazid in tuberculous meningitis (TBM) and its effect on peripheral blood T cell subsets.

The thymus gland is a central lymphoid organ in which developing T cell precursors, known as thymocytes, undergo differentiation into distinct type of mature T cells, ultimately migrating to the periphery where they exert specialized effector functions and orchestrate the immune responses against tumor cells, pathogens and self-antigens. The mechanisms supporting intrathymic T cell differentiation are pleiotropically regulated by thymic peptide hormones and cytokines produced by stromal cells in the thymic microenvironment and developing thymocytes. Interestingly, in the same way as T cells, thymic hormones (herein exemplified by thymosin, thymulin and thymopoietin), can circulate to impact immune cells and other cellular components in the periphery. Evidence on how thymic function influences tumor cell biology and response of patients with cancer to therapies remains unsatisfactory, although there has been some improvement in the knowledge provided by recent studies. Herein, we summarize research progression in the field of thymus-mediated immunoendocrine control of cancer, providing insights into how manipulation of the thymic microenvironment can influence treatment outcomes, including clinical responses and adverse effects of therapies. We review data obtained from clinical and preclinical cancer research to evidence the complexity of immunoendocrine interactions underpinning anti-tumor immunity.

To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) overexpressing indoleamine 2, 3-dioxygenase (IDO) on inflammatory response, T cell subsets and nuclear factor (NF) -κB/ nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3) pathway in abdominal ectopic heart transplantation model rats. Lentivirus vector and gene opening technique were used to construct the overexpressing IDO rat BMSCs, 60 rat models of abdominal ectopic heart transplantation were established, after successful modeling, and they were randomly divided into 4 groups, with 15 rats in each group. No treatment was given after the formation of the blank model, and the mycophenolate group was fed 40 mg/kg mycophenolate group, in the blank BMSCs group, blank BMSS was injected via tail vein 3 days after abdominal heterotopic heart transplantation, and in the IDO group, IDO BMSCs were overexpressed 3 days after abdominal heterotopic heart transplantation by tail vein injection (400 μL per animal. 106 cells). Cardiac function, serum myocardial enzymes, inflammatory factors, T cell subsets, cardiac pathological changes and NF-κB/NLRP3 pathway related protein expression were detected and compared in the four groups. The ejection fraction difference and sequential shrinkage (FS) difference in the IDO group were higher than those in the blank group, mycophenolate group and blank-BMSCs group (P＜0.05). Serum troponin I (cTnI), creatine kinase isoenzyme (CK) -MB, interleukin(IL)-1α, IL-1β, IL-2, γ interferon(IFN-γ), and IL-18 levels, and spleen tissue CD40, CD86, CD80, MHCII, CD45RA, CD45RA combined CD45RB, heart tissue NF-κB, NLRP3, caspase-1 expressions were lower than those in blank group, mycophenolate group and blank-BMSCs group (P＜0.05). The serum IL-10, TGFβ1 and TGFβ1 levels, and the spleen tissue CD274 and Treg expressions were higher than those in the blank group, mycophenolate group and blank-BMSCs group(P＜0.05). HE staining showed that the inflammatory cell infiltration in the IDO group was significantly reduced compared with the blank group, mycophenolate group and blank-BMSCs group. The IDO-BMSCs overexpressing can reduce immune and inflammatory responses, and improve the function of transplanted heart, which may be related to its inhibition of the activation of NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

This multiplex staining panel was developed to differentiate cattle T cells into conventional (CD4 and CD8) and unconventional (γδ‐TCR) subsets as well as their stage of differentiation and activation. The combination of CD45RO and CD62L allows the identification of naïve (TNaïve), central memory (TCM), effector memory (TEM) and terminal effector (TTE) T cells. Activated cattle T cells (TAV) can be identified by the cell surface expression of CD25. This panel was developed using cryopreserved cattle peripheral blood mononuclear cells (PBMCs) and tested on fresh as well as stimulated PBMCs. Therefore, this 8‐color, 10‐parameter flow cytometry panel simultaneously identifies cattle TNaïve, TAV, TCM, TEM, TTE and γδ‐TCR cells. This panel will improve our ability to examine T‐cell response to pathogens and vaccines in cattle including the potential to identify previously undescribed subpopulations. Furthermore, this panel can be readily optimized for other bovid species as many of these reagents are likely to cross react. [ABSTRACT FROM AUTHOR]

T lymphocytes, as a vital component of the adaptive immune system, play a crucial role in maintaining immune health. A thorough investigation of their maturation and aging processes is essential for achieving a comprehensive understanding of the immune system. In this review, we provide an overview of the developmental trajectory of various T cell subsets, encompassing not only the well-known naive, effector, memory subgroups and regulatory T cells, but also delving deeper into unconventional and distinct subgroups such as γδ T cells, mucosal-associated invariant T (MAIT) cells, and natural killer T (NKT) cells. We place particular emphasis on the myriad transformations these cells undergo during the aging process.The advent of single-cell technology in recent years has significantly advanced our understanding of the fundamental mechanisms underlying T cell development and aging. In conclusion, we highlight potential avenues for addressing the persistent challenges encountered in T cell maturation and aging research.

Background: Selective IgA deficiency (SIgAD) is the most prevalent inborn errors of immunity with almost unknown etiology. This study aimed to investigate the clinical diagnostic and prognostic values of lymphocyte subsets and function in symptomatic SIgAD patients. Methods: A total of 30 available SIgAD patients from the Iranian registry and 30 age-sex-matched healthy controls were included in the present study. We analyzed B and T cell peripheral subsets and T cell proliferation assay by flow cytometry in SIgAD patients with mild and severe clinical phenotypes. Results: Our results indicated a significant increase in naïve and transitional B cells and a strong decrease in marginal zone-like and switched memory B-cells in SIgAD patients. We found that naïve and central memory CD4+ T cell subsets, as well as Th1, Th2 and regulatory T cells, have significantly decreased. On the other hand, there was a significant reduction in central and effector memory CD8+ T cell subsets, whereas proportions of both (CD4+ and CD8+) terminally differentiated effector memory T cells (TEMRA) were significantly elevated in our patients. Although some T cell subsets in severe SIgAD were similar, a decrease in marginal-zone and switched memory B cells and an increase in CD21low B cell of severe SIgAD patients were slightly prominent. Moreover, the proliferation activity of CD4+ T cells was strongly impaired in SIgAD patients with a severe phenotype. Conclusion: SIgAD patients have varied cellular and humoral deficiencies. Therefore, T cell and B cell assessment might help in better understanding the heterogeneous pathogenesis and prognosis estimation of the disease. [ABSTRACT FROM AUTHOR]

As previously reported, inflammatory activity initiated by intradermal injection of multiple growing feather (GF)-pulps of a chicken with lipopolysaccharide, and the subsequent periodic sampling of GFs and blood, enables the longitudinal evaluation of in vivo tissue- and systemic-inflammatory activities by ex vivo laboratory analyses. To demonstrate the suitability of this two-window approach to monitor and assess vaccine responses, two groups of chickens were immunized by intramuscular injection of mouse IgG (mIgG), mIgG in alum adjuvant (Alum&mIgG), or PBS-vehicle (Group I and II at 7- and 7- and 11-weeks, respectively). Plasma levels of mIgG-specific antibodies were monitored by ELISA for 28 days post-primary- and secondary-immunizations. To examine the cellular responses, 20 GF-pulps per bird were injected with mIgG on Day-10 or Day-5 post-primary- or -secondary-immunization, respectively. Two GFs were collected before- and at various times (0.25 to 7 days) post-injection for leukocyte population- and cytokine mRNA expression-analyses. The observed primary- and secondary-antibody response profiles were as expected for a T-dependent antigen. Leukocyte- and cytokine-profiles established in GF-pulps revealed temporal, qualitative, and quantitative differences in local naïve, primary, and secondary leukocyte-effector responses to antigen. This study demonstrates the unique opportunity in the avian model to monitor both cell- and antibody-mediated immune responses using minimally invasive techniques. [ABSTRACT FROM AUTHOR]

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral reactivation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found that treatments of HIV-1 infection by suppressive antiretroviral therapy (ART) led to the establishment of latent HIV reservoirs in naïve, central memory and effector memory T cells. Moreover, SECH treatments could clear latent HIV-1 reservoirs in these different T cell subsets of humanized mice. Co-culture studies showed that T cell subsets latently infected by HIV-1, but not uninfected bystander cells, were susceptible to cell death induced by SECH treatments. Our study suggests that the SECH strategy is effective for specific targeting of latent HIV-1 reservoirs in different T cell subsets. [ABSTRACT FROM AUTHOR]

Background: Immunological phenotypes and differentiation statuses commonly decide the T cell function and anti-tumor ability. However, little is known about these alterations in CML patients. Method: Here, we investigated the immunologic phenotypes (CD38/CD69/HLADR/CD28/CD57/BTLA/TIGIT/PD-1) of T subsets (TN, TCM, TEM, and TEMRA) in peripheral blood (PB) and bone marrow (BM) from de novo CML patients (DNCML), patients who achieved a molecular response (MR) and those who failed to achieve an MR (TKI-F) after tyrosine kinase inhibitor (TKI) treatment using multicolor flow cytometry. Results: CD38 or HLA-DR positive PB CD8+TN and TCM cells decreased in the DN-CML patients and this was further decreased in TKI-F patients. Meanwhile, the level of PD-1 elevated in CD8+ TEM and TEMRA cells from PB in all groups. Among BM sample, the level of HLA-DR+CD8+TCM cells significantly decreased in all groups and CD8+TEMRA cells from TKI-F patients exhibited increased level of TIGIT and CD8+ tissue-residual T cells (TRM) from DN-CML patients expressed a higher level of PD-1 and TIGIT. Lastly, we found a significantly decreased proportion of CD86+ dendritic cells (DCs) and an imbalanced CD80/CD86 in the PB and BM of DN-CML patients, which may impair the activation of T cells. Conclusion: In summary, early differentiated TN and TCM cells from CML patients may remain in an inadequate activation state, particularly for TKI-F patients. And effector T cells (TEM, TEMRA and TRM) may be dysfunctional due to the expression of PD-1 and TIGIT in CML patients. Meanwhile, DCs cells exhibited the impairment of costimulatory molecule expression in DN-CML patients. Those factors may jointly contribute to the immune escape in CML patients. [ABSTRACT FROM AUTHOR]

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in primary Sjögren’s syndrome (pSS). The aim of this research was to assess the imbalance of circulating CD8+ T cell subsets. We analyzed blood samples from 34 pSS patients and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages, using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA and CD45. For immunophenotyping of ‘polarized’ CD8+ T cell subsets, we used the following monoclonal antibodies: CXCR5, CCR6, CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of ‘naïve’ CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, rheumatoid factor, the Schirmer test and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS.

The pandemic coronavirus disease 2019 (COVID-19) is a major global public health concern and several protective vaccines, or preventive/therapeutic approaches have been developed. Sinovac-CoronaVac, an inactivated whole virus vaccine, can protect against severe COVID-19 disease and hospitalization, but less is known whether it elicits long-term T cell responses and provides prolonged protection. This is a longitudinal surveillance study of SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels, neutralizing antibody levels (NAb), T cell subsets and activation, and memory B cells of 335 participants who received two doses of CoronaVac. SARS-CoV-2 RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while NAb were measured against two strains of SARS-CoV-2, the Wuhan and Delta variants. Activated T cells and subsets were identified by flow cytometry. Memory B and T cells were evaluated by enzyme-linked immune absorbent spot (ELISpot). Two doses of CoronaVac elicited serum anti-RBD antibody response, elevated B cells with NAb capacity and CD4+ T cell-, but not CD8+ T cell-responses. Among the CD4+ T cells, CoronaVac activated mainly Th2 (CD4+ T) cells. Serum antibody levels significantly declined three months after the second dose. CoronaVac mainly activated B cells but T cells, especially Th1 cells, were poorly activated. Activated T cells were mainly Th2 biased, demonstrating development of effector B cells but not long-lasting memory plasma cells. Taken together, these results suggest that protection with CoronaVac is short-lived and that a third booster dose of vaccine may improve protection. [ABSTRACT FROM AUTHOR]

The function of germinal centers (GCs) is an important factor in the pathogenesis of immunoglobulin G4 (IgG4)–related disease, in which inflammatory and fibrotic processes are controlled by type 2 helper T (Th) cells and regulatory T cells. T follicular helper cells (Tfh), which are present in GCs, regulate GC development, and they consist of Tfh1, Tfh2, and Tfh17 subsets. This study examined the association of Th cell subsets in IgG4-RD and pathogenesis of the disease using whole-slide image analysis for immunohistochemistry. IgG4-related sclerosing sialadenitis (IgG4-SS, n = 19) was characterized by higher numbers of Tfh2 and Tfh17 cells than Tfh1 cells compared to the findings in patients with chronic sialadenitis (n = 18) or Sjögren syndrome (n = 17). The number of Tfh2 cells was significantly associated with all parameters of GC structures and the number of IgG4 + plasmacytes, whereas the number of Tfh1 cells was inversely associated with the aforementioned parameters. Concerning extrafollicular helper T (Teh) cells, among three groups, the Tfh2/Teh2 ratio was highest and the Tfh1/Teh1 ratio was lowest in the IgG4-SS group, which exhibited a characteristically regional distribution of Tfh and Teh subsets, especially higher numbers of Teh2 cells and lower numbers of Teh1 cells in the mantle areas surrounding GCs. Mantle Teh2 cells and central Tfh17 cells were significantly correlated with morphological abnormalities of GCs. Our results indicated that the peculiar regional distribution and altered balance of Tfh and Teh subsets are novel hallmarks of IgG4-SS that are associated with GC formation in IgG4-SS. [ABSTRACT FROM AUTHOR]

Dissecting cellulitis of the scalp (DCS) is a rare skin disease and understudied. The aim of the study was to collect the demographic, clinical features and laboratory tests of patients with DCS in a dermatology outpatient clinic. A cross‐sectional study was conducted in a department of dermatology in Beijing. Patients whose diagnoses have included DCS were selected from July 2021 to December 2021. DCS patients were stratified according to whether they were follicular occlusion triad (FOT) or not. There were 169 patients with DCS included. All 169 patients were male, and the median patient age was 32 years. The most common comorbidities in this study were seborrheic dermatitis (10.65%). Over 1/3 of patients had elevated white blood cell (WBC) and neutrophil counts, and 12 of 18 patients had dyslipidemia. CD8+ T cell counts increased in 15 of 26 patients while CD4+ T/CD8+ T ratios were all normal. DCS mainly affects men in their thirties. More research about DCS is needed to clarify the clinical significance of laboratory tests. [ABSTRACT FROM AUTHOR]

Tuberculosis is a global threat and is still a leading cause of death due to an infectious agent. The infection is spread through inhalation of M. tb containing aerosol droplets. Bacteria after reaching the lung alveoli are engulfed by alveolar macrophages, leading to an immune response. Then, pro-inflammatory cytokines are released by these macrophages, recruiting other antigen-presenting cells like dendritic cells. These cells phagocytose the bacteria and present mycobacterial antigens to naïve T cells. After activation by DCs, T cells differentiate into various T cells subsets, viz. CD4+, CD8+, Th17, Treg, Tfh cells and others display enormous diversification in their characteristics and functions. This review comprises a comprehensive literature on conventional and unconventional T cells, highlighting the polyfunctional T cells as well, their role in controlling TB infection, and their implications in the spectrum of TB infection. While some subsets such as CD4+ T cells are extensively studied, some T cell subsets such as gamma delta T cells and Tfh cells remain poorly understood in the pathophysiology of tuberculosis, despite having significant potential implications. The goal of TB eradication can be assisted by development of better vaccines against TB, which can effectively induce a robust and long-term T cells memory. The same has been discussed in the latter part of this review. BCG being the standalone commercialised TB vaccine so far has its limitations. Strategies for the enhancement of BCG along with novel studies in vaccine development, has also been discussed in great detail. Lastly, T cells display a complex interplay of an adaptive immune response against TB, with activation and enhancement of the innate immune responses. Therefore, it is critical to fully understand the role of various T cells subsets in pathophysiology of tuberculosis to provide better therapeutic inventions and improve patient care. [ABSTRACT FROM AUTHOR]