Production of Autoantibodies in Chronic Hepatitis B Virus Infection Is Associated with the Augmented Function of Blood CXCR5+CD4+ T Cells

PLoS One. 2016 Sep 9;11(9):e0162241. doi: 10.1371/journal.pone.0162241. eCollection 2016.

Abstract

T follicular helper cells (Tfh) provide help to B cells to support their activation, expansion and differentiation. However, the role of Tfh cells in chronic HBV infection is poorly defined. The aim of this research was to examine the function of Tfh cells and whether they are involved in HBV related disease. Blood CXCR5+CD4+T cells and B cells in 85 patients with chronic HBV infection (HBV patients) and health controls (HC) were examined by flow cytometry. The molecule expression in blood CXCR5+CD4+ T cells was detected by real-time PCR. Blood CXCR5+CD4+ T cells and B cells were co-cultured and the production of Ig and cytokines was detected by ELISA. Autoantibodies were detected by indirect immunofluorescence and immunospot assay. We found that blood CXCR5+CD4+ T cells in patients with chronic HBV infection (HBV patients) expressed higher level of activation related molecules and cytokines than that from health controls (HC).In HBV patients, the frequency of blood CXCR5+CD4+ T cells was significantly correlated with serum ALT and AST. We also found that blood CXCR5+CD4+ T cells from HBV patients could induce B cells to secret higher level of immunoglobulin than that from HC. Several autoantibodies, including ANA, ss-A, ss-B, Scl-70, Jo-1, ect, were indeed positive in 65% HBV patients. Among HBV patients, expression of function related molecules was significantly higher in blood CXCR5+CD4+ T cells from patients with autoantibodies than that without autoantibodies. Our research indicated that blood CXCR5+CD4+ T cells from HBV patients were over activated and show augmented capacity to help B cells for antibody secreting, which might correlated with liver inflammation and the production of autoantibodies in extrahepatic manifestations.

MeSH terms

  • Adult
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood*
  • B-Lymphocytes / immunology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Immunophenotyping
  • Male
  • Receptors, CXCR5 / metabolism

Substances

  • Autoantibodies
  • Receptors, CXCR5

Grants and funding

This work was supported by the National Natural Science Foundation of China http://www.nsfc.gov.cn/, [grant numbers 30930082 to HongRen, 31000397 to Yu Lei,81171561 to Peng Hu ], the National Science and Technology Major Project of China http://www.nmp.gov.cn [grant numbers 2008ZX10002-006, 2012ZX1002007001, 2012ZX09303001-001 to Hong Ren], the Key Project of Chongqing Science and Technology Commission http://www.cqwsjsw.gov.cn/ [grant number cstc2012gg-yyjsB10007 to Hong Ren], Chongqing Post-doctor grant http://www.cqhrss.gov.cn/ [grant number XM20120016 to Yu Lei].