CD4^+CXCR5^+ T cells activate CD27^+IgG^+ B cells via IL-21 in patients with hepatitis C virus infection

BACKGROUND： Chronic hepatitis C virus （HCV） infection causes the skewing and activation of B cell subsets, but the characteristics of IgG＋ B cells in patients with chronic hepa- titis C （CHC） infection have not been thoroughly elucidated. CD4＋CXCR5＋ follicular helper T （Tfh） cells, via interleukin （IL）-21 secretion, activate B cells. However, the role of CD4＋CXCR5＋ T cells in the activation ofIgG＋ B cells in CHC patients is not clear. METHODS： The frequency of IgG＋ B cells, including CD27-IgG＋ B and CD27＋IgG＋ B cells, the expression of the activation markers （CD86 and CD95） in IgG＋ B cells, and the percentage of circu- lating CD4＋CXCR5＋ T cells were detected by flow cytometry in CHC patients （n=70） and healthy controls （n=25）. The con- centrations of serum IL-21 were analyzed using ELISA. The role of CD4＋CXCR5＋ T cells in the activation of IgG＋ B cells was investigated using a co-culture system. RESULTS： A significantly lower proportion of CD27＋IgG＋ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27＋IgG＋ B cells, and it contributed to CD27＋IgG＋ B cell apoptosis. Circulating CD4＋CXCR5＋ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4＋CXCR5＋ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27＋IgG＋ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27＋IgG＋ B cells.CONCLUSIONS： HCV infection increased the frequency of CD4＋CXCR5＋ T cells and decreased the frequency of CD27＋IgG＋ B cells. CD4＋CXCR5＋ T cells activated CD27＋IgG＋ B cells via the secretion of IL-21.

Association of FOXP3 Gene Polymorphism with Chronic Hepatitis B in Chinese Population

Objective The forkhead transcription factor FOXP3 is a key molecular which can mediate regulatory T cells immune-related inhibitory functions. Increased levels of FOXP3-positive Tregs in peripheral blood have been proved to be associated with a less favorable prognosis in various inflammatory diseases. It is of great interest to investigate the correlation between single nucleotide polymorphism(SNP) of FOXP3 gene and the susceptibility of chronic hepatitis B(CHB). Methods Two SNPs rs2280883 and rs3761549 of FOXP3 gene in 285 patients with CHB and 295 matched controls were analyzed by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry(MALDI-TOF). Results At rs2280883, there were no significant differences in the distribution of C and T alleles between CHB donors and healthy donors, but at rs3761549, C allele was associated with CHB(P = 0.001). Compared with healthy controls, patients with CHB had high frequencies of TT genotype(73.7%) at rs2280883 or CC genotype(73.6%) at rs3761549 of FOXP3 gene. Patients who carried rs2280883 CC genotype [OR 1.744(95% CI 1.068- 2.848), P = 0.011] or rs3761549 CC genotype [OR 1.633(95% CI 1.146- 2.327), P = 0.0001] had higher risk of suffering from CHB. Stratified analysis showed that rs3761549 CC genotype was significantly associated with high incidence of HBeAg(P = 0.019). Conclusions These results suggested that FOXP3 gene polymorphism at rs2280883 and rs3761549 might be associated with the increased susceptibility to CHB.