Increased proportion of functional subpopulations in circulating regulatory T cells in patients with chronic hepatitis B.

AIM: This study was designed to investigate the levels of circulating regulatory T cells (Tregs), and their functional subpopulations and related cytokines in chronic hepatitis B patients (CHB) and inactive hepatitis B surface antigen carriers. METHODS: The peripheral blood of 24 hepatitis B virus inactive carriers, 26 CHB patients, and 34 healthy controls was collected and analyzed by flow cytometry for Tregs and CD4+ CXCR5+ FoxP3+ follicular regulatory T cells. Interleukin (IL)-10, transforming growth factor-ß, and IL-21 levels in plasma were determined by enzyme-linked immunosorbent assay. Proportions of functional Treg subpopulations were analyzed by staining of Helios, CD45RA and FoxP3, TIGIT, and CD226, and the correlations between Treg subsets and clinical indicators were explored. RESULTS: CD4+ FoxP3+ levels in the peripheral blood of CHB patients were significantly increased, and the inhibitory ability of Tregs in CHB patients for cytokine secretion was stronger, and CD4+ CXCR5+ FoxP3+ follicular Tregs were also significantly higher than inactive carriers and healthy controls. Transforming growth factor-ß and IL-10 in the plasma of CHB patients were significantly higher than those of healthy controls, with IL-21 levels not significantly changed. Circulating CD4+ CXCR5-FoxP3+ Treg cells in CHB patients were positively correlated with hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B virus DNA. The proportions of Helios+ FoxP3+ , CD45RA- FoxP3hi , and CD226- TIGIT+ functional subpopulations in CD4+ CXCR5- FoxP3+ Tregs in CHB patients were significantly increased, and they were significantly correlated with clinical indicators. CONCLUSIONS: Circulating Tregs in CHB patients not only have elevated levels, but their follicular Treg subpopulations are also increased, and Tregs tend to have stronger immunosuppressive functions.

Increased Circulating Th1 and Tfh1 Cell Numbers Are Associated with Disease Activity in Glucocorticoid-Treated Patients with IgG4-Related Disease.

BACKGROUND: This study is aimed at exploring the changes and significance of circulating Th and Tfh cell subsets in glucocorticoid-treated IgG4-RD patients. METHODS: 39 glucocorticoid-treated IgG4-RD patients and 22 healthy controls (HC) were enrolled. Peripheral blood mononuclear cells were separated, and circulating Th and Tfh cell subsets were examined by flow cytometry according to the surface and intranuclear markers. Disease activity was accessed by the IgG4-RD responder index (RI) score. Correlation analyses were conducted between Th/Tfh subset numbers and clinical indicators. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of Th and Tfh subsets to distinguish active IgG4-RD patients from remission IgG4-RD patients. RESULTS: Circulating Th1, Th17, Tfh1, and Tfh17 cells were significantly increased in active IgG4-RD patients compared with HC. Th1 and Tfh1 numbers were positively correlated with serum IgG4 levels in patients with IgG4-RD. Meanwhile, the absolute numbers of circulating Th1 and Tfh1 cells were positively correlated with IgG4-RD RI scores. The areas under the curve (AUC) were 0.8276 for Th1 and 0.7310 for Tfh1, 0.5862 for Tfh2, and 0.6810 for Tfh17. CONCLUSION: Increased circulating Th1 and Tfh1 subsets are related to elevated serum IgG4 levels in active IgG4-RD patients during glucocorticoid treatment, which may play an important role in the course of IgG4-RD disease, and could be potential biomarkers for monitoring disease activity of IgG4-RD.

The Imbalance of Circulating Follicular Helper T Cells and Follicular Regulatory T Cells Is Associated With Disease Activity in Patients With Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum, in which the abnormality of B cells is involved in both its pathogenesis and progression. Follicular helper T cells (TFH) play an important role in assisting the immune function of human B cells in germinal centers, and follicular regulatory T cells (TFR) have the function of inhibiting TFH and germinal center B cell responses. The significance of circulating TFH and TFR in ulcerative colitis (UC) remains unclear. We analyzed peripheral blood of active and stable remission UC patients and found that circulating TFR was significantly decreased while TFH was increased in active UC patients. As to TFH subsets, TFH2 was elevated while TFH17 was decreased in active UC, with IL-4/IL-17A secretion enhanced. Helios+ and CD45RA-FoxP3high TFR cells were decreased while CD226+ and CD45RA+FoxP3int TFR cells were increased in active UC patients. The levels of new memory B cells, plasmablasts and serum IgG were significantly increased in active UC patients, and were positively correlated with TFH and TFH2, and negatively correlated with TFR. Serum CRP and Mayo Clinic scores were positively correlated with TFH and TFH2 but negatively correlated with TFR. Serum IL-12 and IL-21 were up-regulated while IL-10 was down-regulated in active UC. To conclude, an imbalance of circulating TFH and TFR cells is associated with disease activity in UC patients. Our results suggest a new mechanism for TFH and TFR imbalance in the pathogenesis of UC, providing a new perspective for theoretical research and therapeutic strategies for UC.