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

Shuang Zhao1,2, Wen Xu2, Yang-Xin Xie2,3

  • 1Department of infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Insights

Hepatitis B cirrhosis disrupts B cell immunity, altering T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. These changes in Tfh and Tfr cells are linked to disease progression and immune dysfunction in patients.

Area of Science:

  • Immunology
  • Hepatology
  • Cellular Biology

Background:

  • Hepatitis B-associated liver cirrhosis (HBC) significantly alters immune responses, particularly B cell immunity.
  • CXCR5+ CD4+ T cells, encompassing T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, are critical regulators of B cell function.

Purpose of the Study:

  • To investigate the specific roles of CXCR5+ CD4+ T cell subsets in the B cell disruptions observed in Hepatitis B-associated liver cirrhosis.
  • To elucidate the relationship between Tfh and Tfr cells and immune dysfunction in HBC patients.

Main Methods:

  • Analysis of 41 HBC patients and 15 healthy controls.
  • Utilized ELISA, flow cytometry, and cell co-culture techniques.
  • Assessed properties and frequencies of Tfh and Tfr cells, alongside B cell populations and plasma biomarkers.

Main Results:

  • HBC patients exhibited decreased memory B cells and increased plasma B cells.
  • Downregulation of Tfh17 and IL-21+ Tfh cells was observed in HBC patients, correlating with disease severity and plasma biomarkers.
  • Tfr cells were found to inhibit IL-21 secretion by Tfh cells, an effect modulated by IL-10.

Conclusions:

  • Alterations in the frequency and function of Tfh and Tfr cells are implicated in the progression of Hepatitis B-associated liver cirrhosis.
  • These immune cell changes contribute significantly to the immune dysfunction observed in HBC.
Abstract

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