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 (Treg) cells and their functional subpopulations and related cytokines in chronic hepatitis B patients (CHB) and inactive HBsAg carriers. Methods Peripheral blood of 24 HBV inactive carriers, 26 CHB patients and 34 healthy controls were collected and analyzed by flow cytometry for Treg and CD4+CXCR5+FoxP3+ follicular regulatory T (TFR) cells.IL‐10, TGFβ and IL‐21 levels in plasma were determined by ELISA. 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 Levels of CD4+FoxP3+ in peripheral blood of CHB patients were significantly increased, and the inhibitory ability of Treg in CHB patients for cytokine secretion was stronger and CD4+CXCR5+FoxP3+ TFR cells were also significantly higher than inactive carriers and healthy controls. TGFβ and IL‐10 in 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 HBsAg, HBeAg and HBV DNA. The proportions of Helios+FoxP3+, CD45RA‐FoxP3hi and CD226‐TIGIT+ functional subpopulations in CD4+CXCR5‐FoxP3+ Treg cells in CHB patients were significantly increased, and they were significantly correlated with clinical indicators. Conclusions Circulating Treg cells in CHB patients not only have elevated levels, but their TFR subpopulations are also increased and Treg cells tend to have stronger immunosuppressive functions.