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The immunomodulatory role of natural killer (NK) cells has been recognized recently, but its effects on CD4+CD25+ regulatory T cells (Tregs) during chronic hepatitis B (CHB) infection and treatment remain unclear. A total of 116 nucleos(t)ide analogue (NA)-treated CHB patients were included. An inverse correlation between the peripheral frequencies of NK cells and Tregs was found in NA suppressed patients following pegylated interferon-ɑ (PegIFN-ɑ)–based treatment. Furthermore, NK cells suppressed the proliferation and differentiation of Tregs through secreting IFN-γ as was evidenced in the circulation of NA-treated CHB patients as well as in liver of HBV-carrier mouse model. Additionally, the inhibition could be enhanced by PegIFN-ɑ treatment, which was correlated to more vigorous HBV-specific T-cell responses and marked reduction in HBsAg. Our study reveals a novel immunomodulatory mechanism of NK cells and provides a theoretical basis for PegIFN-ɑ as an immunotherapy agent in treating patients with CHB.

Dioscin has been used as a treatment for Hashimoto’s thyroiditis (HT) in China. However, the molecular mechanisms governing the modes of action of dioscin have not been elucidated. In this study, f...

Aims. To determine the role of regulatory cells (Treg) in patients with vulgar psoriasis (VP) and to provide evidence of its possible role in diagnosis, treatment, and measurement of therapeutic efficacy. Material and methods. We studied 60 patients (35 women and 25 men) with VP, ages ranging from 18 to 55 years. Of these, 28 patients had VP in the progressive stage, 19 were stable, and 8 had resolution of the disease. Overall, 42 patients had VP for less than 20 years and 28 patients for 20 years and more. Patients were divided based on VP severity into the following three groups: mild (10 patients), moderate (22 patients), and severe (28 patients). In addition, the amount of Treg was examined before and after narrow-band ultraviolet-B (UVB) therapy in 12 patients with the progressive stage of VP. The healthy donors (HD) group consisted of 22 persons. Results. A reduction in the number of Treg, CD4+CD25+Foxр3+CD127LOW, was observed in the peripheral blood of patients with VP (2.84% 1.00% for patients with VP and 4.02% 0.73% for HD), with an increase in their number with stage transition (2.59% 0.68% in the progressive stage, 2.82% 1.55% in stable, and 3.68% 1.62% in the resolution period). An inverse correlation was determined not only between the number of Treg and the degree of VP severity (r = -0.39) but also with disease duration (r = -0.46). In addition, NB-UVB phototherapy was noted to promote an increase in the amount of Treg.

Background: CXCL4 plays an essential role in the regulation of multiple immune diseases. However, the underlying role of CXCL4 is still not clear in sepsis. Aim: In the present study, we aimed to i...

Background: T regulatory cells (Tregs), through variable mechanisms, play a crucial role in Hepatitis C virus (HCV) chronicity and infection tolerance. A great speculation is posed regarding the le...

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4+CD25+/CD4+ and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan–Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

Attention deficit hyperactivity disorder (ADHD) is a most common mental illness in both children and adults. Our recent studies revealed that high-dose taurine improves hyperactivity in SHR rats by reducing mALFF signal and striatal dopamine uptake. This study further revealed the association between immune factors and hyperactivity in SHR rats fed with high-dose taurine. A positive correlation was detected between systolic blood pressure (SBP) and horizontal locomotion in SHR rats fed with high-dose taurine. Significantly higher striatal Hsp27 and galectin-3 were detected in SHR rats fed with high-dose taurine. Significantly lower IL-2 and IL-6 were detected in SHR rats fed with high-dose taurine, whereas significantly higher IL-10 was detected. Significantly increased splenic CD4+CD25+Foxp3+ regulatory T cells was detected in SHR rats fed with high-dose taurine with a negative correlation. These findings suggest that high-dose taurine reduce hyperactive behavior in SHR rats probably via multifactorial modulation on immune system.

Various genetic factors are controlling regulatory cells T (Treg) cell function, such as miRNAs. Interfering in the miRNA synthesis pathway in Treg cells could result in loss of Tregs' regulatory function, leading to the promotion of inflammatory settings and autoimmunity. This study was designed to investigate the role of miRNA in regulating Treg cells in SLE patients. Treg's frequency was determined using flow cytometry in 100 SLE patients’ and100 healthy controls. Expression of miR-21, miR-24, miR125, miR-146a, miR-148a, and miR-155 was estimated in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction (qRT-PCR). The ROC curve evaluated the diagnostic role of miRNAs in SLE. A significant elevation (p

Background: Among CD4+ T helper (Th) cells, Th17-Treg imbalance is a major pathogenesis of Chronic periodontitis (CP). Treg cells are often considered to play a protective role but they may have plasticity. This study aimed to clarify the regulatory role of Th17-Treg balance in periodontitis and further reveal Treg plasticity.Methods: An experimental periodontitis model was established by ligation of a silk thread and local injection of Pg-LPS. Inflammatory factors in serum and gingival tissues were measured by ELISA and RT-PCR. The degree of alveolar bone absorption was evaluated by micro-CT and histomorphological analysis. Quantities of Treg and Th17 cell and their related gene expression levels were examined. Furthermore, after magnetic bead-sorting spleen Treg cells, their characteristic genes and Th17 cell-related factors were explored at the mRNA level.Results: Inflammatory cytokines in serum and gingival tissue increased significantly in experimental periodontitis, which revealed obvious crestal bone loss around maxillary second molars. Consistently, we found increased secretion of RANKL by osteoblasts, thereby promoting the formation of osteoclasts and enhancing their activity in periodontitis. Further analysis showed that the number of Th17 cells and expression of related genes increased more significantly than Treg cells, demonstrating Treg-Th17 imbalance in periodontitis. Flow cytometry showed that the proportions of Treg cells in the blood and spleen of the periodontitis group was lower than those of the control group. Furthermore, Treg cell-related gene Foxp3 was downregulated and their expression of Th17 cell-related genes Rorc and IL-17A were increased. Conclusions: These results provided evidence that periodontitis may lead to Treg-Th17 conversion, although its mechanisms requires further study.

Background: Several clinical trials on cancer showed a correlation between elevated levels of regulatoryT cells with either poor prognosis or poor response to some therapies. Hence, in this study we tried tomeasure the regulatory T cells (CD4+CD245+) count and to evaluate the program death receptor 1(PD1)as a one of the main suppressive mechanisms that regulatory T cells use in CML patients with differentmolecular response to imatinib therapy. Method: Flow cytometry technique was used to analyze 30 sampleof optimal molecular response of CML patients (BCR-ABL transcripts ? 0.1%) and 30 sample of failuremolecular response patients (BCR-ABL transcripts >1%) with or without hematological failure, in order toassess the CD4+CD25+ T cells (Tregs) and PD1 expression on these cells. Thirty samples age and gendermatched were used as healthy controls. Results: A high proportion of CD4+CD25+ T cells was found infailure groups compared to control and optimal groups(P= 33.7 % washighly significant with high sensitivity and specificity. This value can be used to determine the failure fromthe optimal CML responders. There was no noticeable differences (P= 0.125) in PD1+ expression amongCD4+CD25+ T cells. Conclusion: A high percentage of Treg cells in the failure CML group might be anindication of immune escape of leukemic cells in those patients compared to the other investigated groups.

List of published work using this procedure: Kustrimovic, N., Comi, C., Magistrelli, L., Rasini, E., Legnaro, M., Bombelli, R., Aleksic, I., Blandini, F., Minafra, B., Riboldazzi, G., Sturchio, A., Mauri, M., Bono, G., Marino, F., & Cosentino, M. (2018). Parkinson's disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naïve and drug-treated patients. Journal of neuroinflammation, 15(1), 205. https://doi.org/10.1186/s12974-018-1248-8

Thymic stromal lymphopoietin (TSLP) is a cytokine and is closely related to Interleukin (IL) - 7, and hTSLP can activation through the human thymus dendritic cell in thymic to indirectly promote the differentiation of natural Regulatory T cells (Tregs) of the thymus. In this study, we focused on recombinant TSLP to determine its effects on the differentiation of CD4+CD25-T cells separated from the thymus of myasthenia gravis (MG) patients. Our results demonstrated that exogenous TSLP could increase CD4+CD25+T/CD4+T cells ratio, up-regulate the expression of Foxp3 mRNA and protein expression in CD4+CD25+Treg cells. Furthermore, we found that CD4+CD25+ Treg cells induced by exogenous TSLP could secrete IL - 10, Transforming growth factor (TGF) - β and the ability to inhibit CD4+T cell proliferation improved. These results indicate that TSLP may promote the differentiation of thymic CD4+CD25-T cells of MG patient to CD4+CD25+Foxp3+ regulatory T cells and enhance the function of immune suppression.

Objective: To investigate the effects and mechanisms of different concentrations of CCCP on mitophagy in human peripheral blood regulatory T cells. Methods: Tregs were isolated, identified and then grouped, treating with CCCP at a concentration of 2.5 μM, 5 μM, 10 μM, 20 μM and 40 μM for 24h in an incubator. Flow cytometry detected the reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial quality, and fluorescence microscopy observed the co-localization of mitochondria and lysosomes in each group. Results: The purity of CD4+CD25+Tregs was (93.36 ± 1.87) %. With the increase of CCCP concentration, the level of ROS gradually increased, while the MMP decreased gradually. About the mitochondria and lysosome fusion, the fluorescence intensity of orange (yellow) was the highest when the concentration of CCCP was in the range of 5-10 μM while decreased with the CCCP concentration continually increasing. The mitochondrial quality decreased with the increase of CCCP concentration. However, there was no significant difference between groups C, D and E. The mitochondrial quality of groups F and G were significantly lower than that of group E. Conclusions: With the concentration of CCCP gradually increased, the level of ROS in Treg cells increased, and MMP decreased, which promoted the mitophagy, mitochondrial quality maintains homeostasis; When ROS accumulated, and MMP decreased significantly, the mitophagy was inhibited, and the mitochondrial quality was significantly decreased.

Aim To investigate the impact of physical fitness on the mobilization of CD4+ CD25 - CD39 + and CD4 + CD25 + CD39 + T cells in response to acute exercise. Methods Fifteen high physical fitness (25.3 ± 1.4 years) and 15 low physical fitness (26.1 ± 1.9 years) men performed a single bout of high-intensity interval exercise (HIIE, 10 bouts of 60 seconds at 85% HRmax intercepted by 75 seconds of recovery at 50% HRmax). Blood lymphocytes were isolated before, immediately after and 1 hour after exercise for assessment of cell surface expression of CD25, CD39, and CD73 on CD4+ T cells. Effector memory T cells (mTeff) were identified by CD4 + CD25 - CD39 + coexpression, and memory regulatory T cells (mTReg) were defined as CD4 + CD25 + CD39 + T cells. Results Exercise increased CD4+ and CD4 + CD25 + T cell frequencies immediately after followed by a decrease bellow to baseline values at 1 hour after the bout in both low and high physical fitness groups. At baseline, the proportions of mTeff were higher, while mTreg were lower in low physical fitness individuals. The frequency of mTreg increased immediately after HIIE in both groups, and remained higher 1 hour after the bout. However, high physical fitness individuals presented higher mTreg frequency in all periods evaluated. A significantly mobilization of mTeff cells was identified in both groups immediately after HIIE. High physical fitness individuals displayed a decrease in mTeff cells bellow to baseline, while the frequency of mTeff remained higher in low physical fitness group 1 hour after the bout. The peripheral frequency of CD4 + CD25 + CD73 + T cells increased in a similar way immediately after the bout in both groups, returning to the baseline values 1 hour after exercise. No differences in CD4 + CD25 - CD73 + T cells were observed after HIIE in both groups. Conclusion Our results highlight the impact of physical activity status in the redistribution of CD4+ T cells expressing ectonucleotidases in response to HIIE.

This review focuses on the role of regulatory T cells (Tregs) in the process of carcinogenesis. The controversy of this issue arose due to the increasing therapeutic use of Tregs in humans (inter alia, in the treatment of autoimmune diseases). It is mainly due to potential dangers related to immunosuppressive activity of these cells, especially regarding cancer. The natural function of regulatory T cells (which is the suppression of excessive activity of the immune system) is purportedly linked to an increased risk of cancer initiation. This work brings together and summarizes the most important reports of researchers dealing with this problem and attempts to explain doubts and fears related to Tregs and their uncertain connection with cancer initiation and progression. It is clearly shown that regulatory T cells are associated with acceleration of existing tumors (they are attracted by microenvironments created by cancer cells) but cannot initiate them on their own.

Background Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) as autoimmune diseases arise owing to failure of immunological self-tolerance. One of the mechanisms employed to control these potentially damaging cells are regulatory T cells (Tregs). The importance of Tregs is underscored by the overwhelming inflammation and autoimmunity that result from their absence. Forkhead box p3 (FoxP3) is an important regulator of Treg function, and the expression of FoxP3 correlates with the expression of other Treg-associated markers such as CD25 and CTLA-4. Aim To investigate the frequency of FoxP3+ CD4+ CD25+high cells (Tregs) in peripheral blood from patients with SLE and those with RA. Patients and methods A total of 25 patients with SLE (15 patients with active SLE and 10 patients with inactive SLE), 25 patients with RA (15 patients with active RA and 10 patients with inactive RA), and 10 age-matched and sex-matched healthy controls were enrolled in the study. Patients underwent clinical and laboratory assessment. The frequency of Tregs was determined by flow cytometry. Results The distribution of FoxP3+ CD4+ CD25+high cells (Tregs) revealed a highly significant decrease in the frequency of Treg in patients with SLE compared with healthy controls. Moreover, patients with active SLE showed significantly lower Tregs percent when compared with inactive group. Moreover, the distribution of FoxP3+ CD4+ CD25+high cells (Tregs) revealed a high significantly decrease in the frequency of Treg in patients with RA compared with healthy controls. Conclusion CD4+ CD25+ FoxP3 Tregs (as a percent of total CD4 cells) were significantly lower in patients with SLE and those with RA when compared with healthy controls.

Background: The involvement of CD4+CD25+ regulatory T cells (CD4+CD25+ TRegs) in allergic diseases was reported previously. However, it remains unclear whether CD4+CD25+ TRegs are involved in allergic rhinitis (AR). Methods: Fresh whole blood from 20 patients with AR and 16 healthy donors was used to investigate the frequency of CD4+CD25+ and CD4+CD25hi Treg cells using flow cytometry. In addition, serum total IgE (IU/mL) levels were determined using enzyme-linked immunosorbent assays. Results: Patients with AR had fewer CD4+CD25+ Treg cells (2.80 ± 1.36% vs. 3.94 ± 0.97%, P < 0.01) and CD4+CD25hi TRegs (1.53 ± 0·62% vs. 2.00 ± 0.52%, P < 0.05) than control subjects. The number of CD4+CD25+ and CD4+CD25hi TRegs was correlated negatively with total immunoglobulin E levels (r = –0.79, P < 0.01 and r = –0.61, P < 0.01, respectively). Conclusion: Deficient regulatory T cells might play a role in the development of AR.

Multipl Skleroz patogenezinde otoimmunitenin ortaya cikisinda periferik immun toleransin bozulmasi onemli rol oynamaktadir. Immun toleransin saglikli isleyisinde regulatuvar T hucreleri ise anahtar rol oynamaktadir. FoxP3 ise regulatuvar T hucreler yeterli ekpresyonu icin transkripsiyon faktoru olarak gorev almaktadir. Biz bu calismayla Mc Donald’s kriterlerine gore klinik olarak kesin MS tanisi almis 12 RRMS (relapsing Remitting Multipl skleroz), 11 SRMS ( Sekonder Relapsing Multipl skleroz), 8 atak RRMS hastasi olmak uzere toplam 31 hasta ile 12 saglikli kontrol gurubunun regulatuvar T hucre alt tipleri hematoloji laboratuarinda akim sitometrisi ile analiz ederek total CD4(+) T lenfosit icerisindeki yuzdeleri ve FoxP3 ekspresyonunu karsilastirdik. Atakli 8 RRMS hastasinin ise 7 tanesi 1000 mg/ gun IVMP tedavisinden once ve tedaviden sonra kendi icinde karsilastirildi. Sonuclar istatiksel olarak degerlendirildi. Regulatuvar T hucre profili CD4(+) CD25(+), CD4(+) foxP3(+), CD4(+) CD25(+) foxP3(+),CD4(+) CD25(+) foxP3(-), ve CD4(+) CD25(-) foxP3(+) karsilastirildi, hastalar ve kontrol grubu arasinda anlamli fark bulunmadi (p>0.005). Atak oncesi ve atak sonrasi IVMP tedavisi sonrasi 7 hastanin regulator hucre profilleri ve foxP3 ekspresyonu arasinda anlamli fark saptanmadi (p>0.05). Ancak, yuksek doz intravenoz metilprednizolon (IVMP) tedavisinin regulator hucre alt tipleri icinde hafif bir sayisal artis neden oldugu gozlenmistir. Regulatuvar T hucrelerin MS imunopatogenezinde sayisal yeterliligi yaninda islevsel ozelliklerinin onemli rol oynadigi dusunuldu.

Objective Early detection of severe forms with unfavorable outcome is the cornerstone that could provide reduction of morbidity and mortality in acute pancreatitis (AP). Methods The percentage of circulating CD4CD25CD127 regulatory T-cells (Tregs) was determined at admission, on the 48th hour, and on the fifth day in 72 patients with AP. We divided patients in 2 groups-Sev1, which includes 19 patients (26.4%) with moderate AP and 39 patients (54.2%) with mild disease, and Sev2, which includes 14 patients (19.4%) with severe AP. Seven patients (9.7%) developed septic complications. The mortality in our group was 9.7%. Results The patients in Sev2 had higher percentage of Tregs at admission and on the fifth day compared with patients in Sev1 (P = 0.007 and P = 0.033, respectively). There was no significant difference in percentage of Tregs at admission, on the 48th hour, and on the fifth day in patients who developed and did not develop infected necrosis (P = 0.50, P = 0.72, and P = 0.92, respectively). Patients with poor outcome had elevated percentage of Tregs on the fifth day (P = 0.045). Conclusions The percentage of circulating Tregs may be implicated in the development of early immune suppression in AP. Elevated percentage of circulating Tregs at admission in AP is an independent prognostic biomarker for severe disease.

The effect of anti-CD25 monoclonal antibody (anti-CD25 mAb) on the protection efficacy of Schistosoma japonicum 26 kDa GST (glutathione-S-transferase) vaccine was evaluated. Mice were immunized with GST before infection with S. japonicum cercariae and then injected with anti-CD25 mAb. The worm reduction rate was promoted from 24.18% in mice with GST immunization to 47.09% in mice with GST plus anti-CD25 mAb. Compared with the control group, the percentages of splenic CD4+CD25+Foxp3+ regulatory T cells (Tregs) were significantly lower after administration of anti-CD25 mAb; meanwhile, elevated levels of IFN-γ and IL-2 were secreted by splenocytes. These results indicate that the poor protective efficacy of the GST vaccine against S. japonicum results from the presence of CD4+CD25+Foxp3+ Tregs, while anti-CD25 mAb can partially block CD4+CD25+Foxp3+ Tregs and thus enhance the protective efficacy of the GST vaccine.

Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at 2 years. Among lung-transplanted patients between January 2009 and July 2011, only patients with sufficient Treg measurements were included into the study. Tregs were measured immediately before lung transplantation, at 3 weeks and 3, 6, 12, and 24 months after transplantation and were defined as CD4+ CD25high T cells and further analyzed for CTLA4, CD127, FoxP3, and IL-2 expressions. Between January 2009 and July 2011, 264 patients were transplanted at our institution. Among the 138 (52%) patients included into the study, 31 (22%) developed CLAD within 2 years after transplantation. As soon as 3 weeks after lung transplantation, a statistically significant positive association was detected between Treg frequencies and later absence of CLAD. At the multivariate analysis, increasing frequencies of CD4+ CD25high CD127low , CD4+ CD25high FoxP3+ and CD4+ CD25high IL-2+ T cells at 3 weeks after lung transplantation emerged as protective factors against development of CLAD at 2 years. In conclusion, higher frequencies of specific Treg subpopulations early after lung transplantation are protective against CLAD development.

Aim To investigate T-cell subpopulations in peripheral blood of human parvovirus B19 DNA-positive (B19+) and -negative (B19-) patients with rheumatoid arthritis (RA) and healthy persons. Patients and methods Blood samples were collected from 115 patients with RA and 47 healthy volunteers; 27 patients with RA and nine controls were B19+ Cluster of differentiation (CD) 4, 8, 25 and 45RA were analyzed on blood cells. CD25 expression on CD4+CD45RA+, CD4+CD45RA-, CD8+CD45RA+, CD8+CD45RA- subsets were analyzed by flow cytometry. Results The percentage of CD25low and CD25hi cells was increased on CD4+CD45RA+, CD4+CD45RA- T-cells and the percentage of CD25+ cells was increased on CD8+CD45RA+, CD8+CD45RA- T-cells of B19+ patients with RA in comparison with B19- patients and controls. Conclusion Raised levels of CD4 and CD8 regulatory T-cells in B19+ RA patients could cause down-regulation of antiviral clearance mechanisms and lead to activation of persistent human parvovirus B19 infection in patients with RA.

Background Regulatory T cells (Tregs) play a crucial role in maternal-fetal tolerance, but little is known about the characteristic of Tregs in peripheral blood (PB), maternal-fetal interface and cord blood (CB) in normal and complicated pregnancies with preeclampsia (PE), gestational diabetes mellitus (GDM) and premature rupture of membranes (PROM). Methods PB, retro-placental blood (RPB), and CB were collected immediately after delivery in women with normal full-term pregnancy (NP), PE, GDM, and PROM. The proportion of CD4 + CD25 + CD127 low/- T cells (Tregs) and the expression of PD-1, GITR, HLA-G and CTLA-4 on T cell subsets were investigated by flow cytometric analysis. The data were analyzed based on sample origins (PB, RPB, and CB) and the obstetrical study groups (NP, PE, GDM, and PROM). Results The proportions of Tregs in PB, RPB, and CB from NP were significantly higher than the other obstetrical groups (P < 0.01, respectively). However no significant differences were present among the PE, GDM and PROM groups (P = NS). The proportion of PD-1 + and GITR + Tregs in RPB and PB as well as PD-1 + Tregs in CB from NP were significantly higher than those of the same origin in each obstetrical study group (P < 0.01, respectively). There were no differences in HLA-G + and CTLA-4 + Tregs between different origins in each obstetrical study group. In NP, the proportion of PD-1 + Tregs was significantly decreased in CB as compared to those of PB and RPB (P < 0.05, respectively). Among the four groups, the proportion of GITR + Tregs were significantly higher in PB as compared to those of CB and RPB (P < 0.01, respectively). The proportion of HLA-G + Tregs in PB was significantly lower than that of CB and RPB (P < 0.01, respectively). The proportion of CTLA-4 + Tregs had no significant differences (P = NS). Conclusions In conclusion, the proportion and characteristics of Tregs vary in the maternal, fetal and maternal-fetal junction at the time of delivery. The different feature and density of Tregs in maternal and fetal tissue may suggest the multiple and complicated roles of Tregs during pregnancy.

This SOP describes a closed system for isolating GMP-grade CD4+CD25+ T cells from non-mobilized leukapheresis collections (nMLCs), independent of a clean room in a certified GMP premises, by using CliniMACS format GMP grade reagents (CD25-labeled magnetic beads with/without pre-depletion of CD8+ T cells and CD19+ B cells), a GMP grade-A laminar hood and CliniMACS cell processing system.

An increased number of regulatory T (Treg) cells has been reported in patients with HTLV-1 and Strongyloides stercoralis co-infection, suggesting the contribution of these cells to worm survival. As Strongyloides infections have been found to be highly prevalent in chronic alcoholics, we investigated the effect of abusive ethanol ingestion on the induction of Treg cells in alcoholic patients with Strongyloides infection. Treg cells were assessed by flow cytometry in the peripheral blood of 12 healthy non-alcoholic (control) and 14 alcoholic patients (alcoholic) without Strongyloides infection and five non-alcoholics (controlSs) and five chronic alcoholics (alcoholSs) with Strongyloides infection. The results showed significantly higher frequencies of Treg cells in the alcoholic, controlSs and alcoholSs group patients than in the control group patients. However, the frequencies of Treg cells did not differ between the alcoholSs and controlSs groups. In conclusion, our results demonstrate that ethanol consumption induced an increase in the number of circulating Treg cells in chronic alcoholics in this study but was unable to potentiate the induction of these cells in alcoholics with Strongyloides infection.

The critical contribution of CD4+CD25+Foxp3+ T-regulatory cells (Treg) to immune suppression in the tumor microenvironment is well-established. Whereas the mechanisms that drive the generation and accumulation of Treg in tumors have been an active area of study, the information on their origin and population dynamics remains limited. In this review, we discuss the ontogeny of tumor-associated Treg in light of the recently identified lineage markers.

Multiple sclerosis (MS) is an autoimmune disease characterized by defect in regulatory function of CD4+CD25+ T cells. We demonstrated difference in proportion of regulatory T cells CD4+CD25+FoxP3+CD127low (Tregs) within the same patients’ relapse and remission. Proportion of peripheral Tregs (pTregs) dropped almost two times in the relapse compare to remission. Levels of pTregs in patients’ remission were lower than in healthy donors. Suppressive ability of pTregs was decreased in MS patients compared to healthy donors. Injections of expanded ex vivo autologous Tregs (eTregs) could be helpful in bringing up the level of Tregs in patients’ blood. We developed a simple method for ex vivo expansion of autologous Tregs within a short period of time. The final pool of cells consisted of 90-95% eTregs. When we started the culture with 10-20 × 106 CD4+ T cells, we yield 300-400 × 106 eTregs in a week. Expression of FoxP3 and Helios was calculated by two methods. Expanded ex vivo patients’ and donors’ Tre...

Background Allergic Rhinitis (AR) is the most common immunological disease that has been associated with inflammatory responses and is characterized by sneezing. Previous studies found that AR's allergen exposure significantly induces plasma cells and reduces regulatory T (Treg) cells, a population that contributes to control AR. Therefore, upregulating Treg expression can regulate plasma cells leading to inhibit sneezing in AR. Mesenchymal stem cells (MSCs) are multipotent stem cells that have the immunoregulatory and antiinflammation ability by secreting various cytokines including IL-10 and TGF-β which potent as a promising therapeutic modality for allergic airway diseases, including AR. Objective To investigate the role of MSCs in generating CD4+, CD25+, and Foxp3+ Regulatory T cells associated with suppressing plasma cell in AR model. Methods In this study, fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and MSCs treatment group). OVA nasal challenge was conducted daily from day 15 to 21, and MSCs (1x106) were administrated intraperitoneally to OVA-sensitized rats on day 21. Sneezing was observed from day 22 to 28. The rats were sacrificed on day 22 and day 28. The expression of CD4+ CD25+ Foxp3+ in Treg and plasma cells was analyzed by flow cytometry assay. Results This study showed that the percentage of plasma cell and sneezing times significantly decreased in MSCs treatment. This finding was aligned with the significant increase of CD4+CD25+Foxp3+ Treg level. Conclusion MSCs administration suppress plasma cells population and sneezing times by up regulating Treg to control AR.

Background It was found that regulatory T cells (Tregs) importantly affect the maintenance of the kidney graft. However, Tregs are a heterogeneous population with less to more suppressive activity. The aim of this study was to determine the effects of different subsets of Tregs, as well as their ratio to effector T cells (Teff), on kidney transplantation outcomes. Methods A total of 58 participants were enrolled in this study and divided into four groups: (i) first kidney transplant recipients (stable 1); (ii) second kidney transplant recipients (stable 2); (iii) transplant recipients with acute rejection (AR); and (iv) healthy control subjects. By using flow cytometer, the frequencies of CD4+ CD25++ CD45RA− Foxp3hi activated Tregs (aTregs), CD4+ CD25+ CD45RA+ Foxp3lo resting Tregs (rTregs), CD4+ CD25+ CD45RA− Foxp3lo non-suppressive T cells, CD4+ CD25+ Foxp3− cells Teff, and total Tregs were analyzed in all subjects. Results The frequency of aTregs (as well as the ratio of aTregs/Tregs) was significantly lower in the AR patients than the other three groups. In contrast to AR patients, stables 1 and 2 had a higher aTreg/Treg ratio than those in the control group. Although patients with AR had a significantly lower total Tregs than the other three groups, the balance of total Tregs and Teff was similar between patients with and without AR. Conclusion Patients with AR had poorer immunoregulatory properties than those with normal graft functioning, as well as those in the control group. These reduced immunoregulatory properties in patients with AR could lead to graft rejection.

Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation and induced by donor T cells contained in the graft. Current GVHD prevention and treatment strategies all aim at the elimination or functional inactivation of donor T cells. The rediscovery of suppressor T cells, now called regulatory T cells (Treg), and the illustration of their pivotal role for the maintenance of peripheral self-tolerance under physiologic conditions raised the question, whether generalized T-cell inactivation always represents the best strategy for the prevention of GVHD. Because such treatments also impair suppressive T-cell populations, the development of central and peripheral tolerance may also be hampered by pharmacologic immunosuppressants and thus contribute to the perpetuation of GVHD. Here we summarize the experimental and clinical findings about the role of thymus-derived Treg cells in allogeneic SCT and GVHD.

Experimental autoimmune neuritis (EAN) induced by peripheral nerve myelin (PNM) is self-limiting and re-immunization with PNM does not re-activate disease. This study showed inhibition of EAN by CD4+CD25+T cells both from sensitized hosts or from naive hosts after ex-vivo activation by PNM and rIL-2. Transfer of naive CD4+CD25+T cells has no effect on EAN, nor did naive CD4+CD25+T cells activated with rIL-2 and renal tubular antigen. Culture of naive CD4+CD25+Treg with rIL-2 and PNM induced mRNA for the IFN-gamma receptor. We showed naive CD4+CD25+T cells activated by specific auto-antigen and rIL-2 produced more potent antigen-specific Treg that may have therapeutic potential.

Effects of anesthesia methods on immune function in patients with lung cancer undergoing radical operation were investigated. A total of 122 patients undergoing radical resection of lung cancer who were treated in Zhejiang Cancer Hospital from September 2013 to April 2016 were randomly divided into the combined anesthesia group and the intravenous anesthesia group, with 61 cases in each group. The patients in the combined anesthesia group were given intravenous combined epidural anesthesia. Patients in the intravenous anesthesia group were given intravenous anesthesia. The change of CD3+, CD4+ and CD4+CD25+ at time-point T0 (before anesthesia), T1 (the time of anesthesia), T2 (after operation), T3 (24 h after operation), T4 (72 h after operation) were compared between the two groups. The levels of CD3+, CD4+ and CD4+CD25+ at T1, T2, T3 and T4 in the combined anesthesia group were higher than that in the intravenous anesthesia group (P

A rapidly growing evidence showed that regulatory T cells (Tregs) play a crucial role in tolerance to coagulation factors and may be involved in the pathogenesis of inhibitor formation in patients with hemophilia. We determined the percentage of Tregs (CD4CD25CD127) in 45 children with hemophilia A compared with 45 healthy controls, and assessed their relation to the clinical characteristics of patients and factor VIII (FVIII) inhibitors. Patients were studied stressing on frequency of bleeding attacks, joint pain, history of viral hepatitis, and the received therapy (FVIII precipitate/cryotherapy). FVIII activity and FVIII inhibitors were assessed with flow cytometric analysis of CD4CD25CD127 Tregs. According to residual FVIII activity levels, 30 patients (66.7%) had mild/moderate hemophilia A, whereas 15 (33.3%) patients had severe hemophilia A. The frequency of Tregs was significantly lower among all patients with hemophilia A compared with controls (2.59 ± 1.1 versus 3.73 ± 1.12%; P = 0.002). Tregs were significantly decreased among patients with FVIII inhibitors compared with the inhibitor-negative group (P < 0.001). Patients with hematuria or severe hemophilia A had lower Tregs levels than those without (P = 0.34 and P = 0.011, respectively). A significant positive correlation was found between the percentage of Tregs and FVIII among hemophilia A patients. ROC curve analysis revealed that the cut-off value of Tregs at 1.91% could differentiate patients with and without FVIII inhibitors, with a sensitivity of 100% and a specificity of 91.3%. We suggest that alteration in the frequency of Tregs in young patients with hemophilia A may contribute to inhibitor formation and disease severity.

Transplant tolerance induced in adult animals is mediated by alloantigen-specific CD4+CD25+ T cells, yet in many models, proliferation of CD4+ T cells from hosts tolerant to specific-alloantigen in vitro is not impaired. To identify changes that may diagnose tolerance, changes in the patterns of proliferation of CD4+, CD4+CD25+, and CD4+CD25− T cells from DA rats tolerant to Piebald Virol Glaxo rat strain (PVG) cardiac allografts and from naïve DA rats were examined. Proliferation of CD4+ T cells from both naïve and tolerant hosts was similar to both PVG and Lewis stimulator cells. In mixed lymphocyte culture to PVG, proliferation of naïve CD4+CD25− T cells was greater than naïve CD4+ T cells. In contrast, proliferation of CD4+CD25− T cells from tolerant hosts to specific-donor PVG was not greater than CD4+ T cells, whereas their response to Lewis and self-DA was greater than CD4+ T cells. Paradoxically, CD4+CD25+ T cells from tolerant hosts did not proliferate to PVG, but did to Lewis, whereas naïve CD4+CD25+ T cells proliferate to both PVG and Lewis but not to self-DA. CD4+CD25+ T cells from tolerant, but not naïve hosts, expressed receptors for interferon (IFN)-γ and IL-5 and these cytokines promoted their proliferation to specific-alloantigen PVG but not to Lewis or self-DA. We identified several differences in the patterns of proliferation to specific-donor alloantigen between cells from tolerant and naïve hosts. Most relevant is that CD4+CD25+ T cells from tolerant hosts failed to proliferate or suppress to specific donor in the absence of either IFN-γ or IL-5. The proliferation to third-party and self of each cell population from tolerant and naïve hosts was similar and not affected by IFN-γ or IL-5. Our findings suggest CD4+CD25+ T cells that mediate transplant tolerance depend on IFN−γ or IL-5 from alloactivated Th1 and Th2 cells.

This experiment was aimed to determine the bioactivity of ethanolic extract of propolis (EEP) against the changes in the quantity of CD4 + CD25 + and B220 + lymphocytes and determine the optimal dose of EEP to increase the number of CD4 + CD25 + and B220 + cells in Balb/c mice. Balb/c mice were divided into four treatment groups: control treatment, treatments of EEP at a dose of 50 mg.kg -1 , 100 mg.kg -1 , and 200 mg.kg -1 body weight of mice. All mice were dissected after two weeks post treatment. Profiles of lymphocytes from the spleen expressing CD4 + CD25 + and B220 + cells were analyzed by flowcytometry using CellQuest software. Data was analyzed by Kruskall Wallis and Mann Whitney statistical test with P