CXCR5 + CD4 + T cell subsets and their relationship to immune dysfunction in chronic hepatitis B associated liver cirrhosis

Shuang Zhao, Wen Xu, Yang-Xin Xie, Wei-Wei Chen, Min Zhao
Journal of Gastroenterology and Hepatology 2019 September 13

OBJECTIVE: Hepatitis B associated liver cirrhosis (HBC) leads to profound alterations of immune systems, especially disruptions of B cell immune responses. CXCR5+CD4+ T cells (including T follicular helper cells (Tfh) and T follicular regulatory cells (Tfr)) are responsible for the regulation of B cell functions. The aim of this study was to dissect the roles of CXCR5+CD4+ T cell subset in B cell disruption caused by HBC.

METHODS: 41 patients with HBC and 15 healthy controls (HC) were enrolled in this study. ELISA, flow cytometric analysis and cell coculture were performed to analyze the properties of Tfh and Tfr.

RESULTS: We observed significantly decreased memory B cells (MB) and increased plasma B cells (PLC) in HBC patients, as well as significant upregulation of LPS binding protein (LBP) and soluble CD14 (sCD14) in plasma of decompensated HBCs patients. The downregulation of Tfh17 was observed in HBC patients with spontaneous bacterial peritonitis (SBP) compared to those without. The decrease of Tfh17 was paralleled with Child-Pugh grade and negatively correlated with PLC and sCD14 in HBC patients. IL-21+Tfh of HBC patients was also downregulated compared to HCs, and it was positively correlated with MBs and the upregulation of IL-10+Tfr. It was then revealed that Tfr could inhibit the secretion of IL-21 by Tfh, and the blocking of IL-10 could diminished this effect.

CONCLUSIONS: The changes of the frequency and function of Tfh and Tfr may play an important role in disease progression and immune dysfunction of HBC.

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