Tfh Cells In Peripheral Blood Research Articles

Increased CD4+CXCR5+T follicular helper cells in diabetic nephropathy

Background: T follicular helper (Tfh) cells are known to regulate humoral immune response. In this study we examined the correlation of different subsets of peripheral blood Tfh cells in patients with diabetic nephropathy (DN). Methods: A total of 23 DN patients and 15 healthy controls (HC) were investigated for various subsets of Tfh cells by flow cytometry. The molecules ICOS+, PD-1+, CD28+, CD154+, IL-21+, IFN-γ+, IL-4+, IL-17+ Tfh cells were examined. The subsets of B cells were investigated by flow cytometry. The levels of 24 h urinary protein and estimated glomerular filtration rate (eGFR) were calculated. A potential correlation between the number of different subsets of Tfh cells, B cells and DN, was assessed. Results: The circulating CD4+CXCR5+PD-1+, PD-1+CD154+, PD-1+CD28+, PD-1+IL-21+, PD-1+IL-4+, PD-1+-IL-17+-Tfh cell counts, CD38+CD19+, CD38+CD19+CD40+ B cells and plasma levels of IL-21 were significantly increased in DN patients (p < 0.05), as compared to that in the HC group. Furthermore, the circulating CD4+CXCR5+PD-1+ Tfh cell counts negatively correlated with eGFR; Tfh cell counts positively correlated with 24 h urinary protein concentration in DN patients. Post-treatment, there was a significant reduction in the CD4+CXCR5+PD-1+ Tfh cell counts and its subsets, with a corresponding decrease in plasma levels of IL-6 and IL-17A (p < 0.05) in DN patients, as compared to the HCs. Conclusion: An increased number of CD4+CXCR5+PD-1+ Tfh cells were observed in DN patients, which may be new targets for intervention in DN.

T follicular helper cells in patients with acute schistosomiasis.

BackgroundThe role of T follicular helper (Tfh) cells in schistosome infection is not fully defined. In a previous study, a higher frequency of circulating PD-1+CXCR5+CD4+ Tfh cells was observed in patients with chronic schistosomiasis relative to healthy controls (HCs) and it correlated positively with the level of soluble egg antigen (SEA) specific antibodies in serum. However, the function of Tfh cells in patients with acute schistosomiasis remains elusive; this was investigated in the present study.MethodsThe frequency of circulating Tfh cells and the expression of inducible T cell co-stimulator (ICOS), programmed cell death 1 (PD-1) and B cell subsets were analyzed in 12 patients with acute schistosomiasis and 10 HCs by flow cytometry. The expression of Bcl6, c-Maf and IL-21 mRNA were detected by quantitative real-time reverse transcriptase PCR (qRT-PCR). The concentration of serum IL-21 and IgG specific to Schistosoma japonicum antigen were then determined by enzyme linked immunosorbent assay (ELISA). Correlations between PD-1+CXCR5+CD4+ Tfh cells, memory B cells and IgG specific to S. japonicum were analyzed by Spearman’s rank correlation.ResultsThe frequency of PD-1+CXCR5+CD4+ Tfh and memory B cells was increased in acute schistosomiasis patients relative to HCs. Moreover, the levels of IL-21 in serum and the expression of IL-21 mRNA were higher in acute schistosomiasis patients. However, there was no significant correlation between PD-1+CXCR5+CD4+ Tfh cells, memory B cells and IgG specific to S. japonicum antigen in patients with acute schistosomiasis.ConclusionsPD-1+CXCR5+CD4+ Tfh cells in peripheral blood are involved in the immune response of patients with acute schistosomiasis. Understanding the immunological mechanism is helpful for the development of vaccination strategies to control schistosomiasis.

Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

Enhancement of CD154/IL4 proliferation by the T follicular helper (Tfh) cytokine, IL21 and increased numbers of circulating cells resembling Tfh cells in chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) cells encounter T-cells and proliferate in response to T-cell signals in the lymph node microenvironment. In this report we determined interleukin 21 (IL21) function in CLL and showed that IL21 and interleukin 4 (IL4) act co-operatively to promote leukaemic cell proliferation without apoptosis or differentiation We further show that IL21 increased side population (SP) cells, which are associated with resistance to chemotherapy and increased self-renewal capacity in CLL. IL21 and IL4 are the major cytokines produced by the recently described CD4(+) T follicular helper (Tfh) cell subset. Determination of Tfh cells in peripheral blood showed that patients had significantly increased numbers as compared to normal subjects although no association was found between Tfh numbers and IGHV gene mutational status or clinical stage. Our data suggests that the Tfh cytokines, IL4 and IL21, contribute to driving leukaemic cell proliferation in the lymph node microenvironment, and may contribute to the specific production of cells resistant to conventional chemotherapy. We suggest that increased circulating Tfh cells is a component of T-cell dysregulation in CLL. Our findings have implications for the therapeutic use of IL21.

Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4+ and CD8+T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS+TFH-cells in peripheral blood from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor+CD4+T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN+ and CD83+B-cells in SPMS. ICOS+TFH-cells and DC-SIGN+B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4+T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients) had increased expression of TFH-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings from pathology studies which, along with the correlation between activated TFH- and B-cells and disease progression, suggest a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS.

Follicular helper T cells in immune homeostasis

Follicular helper T cells in immune homeostasis

The abnormality and clinical significance of follicular helper T cells and T helper 9 cells in patients with rheumatoid arthritis

Objective To investgate the expression of Tfh and Th9 in the peripheral blood of rheumatoid arthritis ( RA),and to analyze the relationship between those cells and disease activity,organs of involvement,ect.,and to underly the possible immunological mechananism of RA.Methods Peripheral blood Tfh cells and Th9 cells,define as the CD4+ CXCR5 + ICOS+ and CD3 + CD8+ IL-9+ population,were examined by flow cytometry in 36 patients with RA and 22 case of age-and gender-matched health controls.According to 28-joint Disease Activity Score (DAS28),patients were divied into two groups:high disease activity(n=22),moderate disease activity(n=14).And then to analyzed the correlation among the Tfh,Th9 and clinical data of RA,such as ESR,CRP,RF,the number of tender joints,the number of swollen joints and bone destruction,etc..While to analyzed the correlation between Th9 and Tfh.Results The expression of Tfh (Z=-6.082,P=0.000) and Th9 (0.989±0.498 vs 0.213±0.084,t=13.063,P =0.000 )in PBMCs of RA was significantly higher than normal controls.Meanwhile,the expression of Tfh ( 3.880 ±1.255 vs 2.678±1.022,t=2.990,P=0.005 ) and Th9( 1.181 ±0.523 vs 0.686±0.254,t =4.043,P=0.000) in high activity of group were higher than those moderate.The percentage of Tfh and Th9 in the two groups were all signifieantly higher than controls(P＜0.01 ),There was a positive correlation with Tfh and DAS28 ( r =0.571,P=0.000),ESR ( r =0.375,P =0.029),CRP( r =0.357,P =0.032 ),the number of tender joints ( r=0.598,P =0.000 ),RF ( r =0.421,P =0.023 ) and anti-CCP ( r =0.421,P =0.023 ).There were no relationship with Tfh and course,morning stiffness,the number of swollen joints,bone erosion and the abnormal of EKG.There was a positive correlation with Th9 and DAS28( r=0.461,P=0.005 ),ESR(r=0.347,P=0.042),CRP(r=0.384,P=0.210),the number of tender joints(r=0.341,P=0.042),the number of swollen joints (r =0.347,P=0.038 ) and RF( r =0.379,P =0.025 ) respectively.There were no relationship with Th9 and course,morning stiffness,CCP,the abnormal of EKG,bone erosion.There was a positive correlation with Tfh and Th9 (r=0.727,P =0.000),Conclusion The expression of Tfh and Th9 were increase significantly,which those cells were close relationship with the disease activity and some data,These results indicate that the abnormality of Tfh and Th9 may play an important role in the pathogenesis of RA. Key words: Rheumatoid arthritis ; Follicular helper T cells ; T helper 9 cells ; Pathogeny

Chemokines and their receptors in t cell migration

Chemokines and their receptors in t cell migration