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

ABSTRACT

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.