CXCR5+ CD8+ T Cells Indirectly Offer B Cell Help and Are Inversely Correlated with Viral Load in Chronic Hepatitis B Infection

DNA Cell Biol. 2017 Apr;36(4):321-327. doi: 10.1089/dna.2016.3571. Epub 2017 Feb 3.

Abstract

Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5+ CD8+ T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5+ CD8+ T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5+ CD8+ T cells in peripheral blood, in which CXCR5+ CD8+ T cells were negatively correlated with the frequency of CXCR5+ CD4+ T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5+ CD8+ T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5- CD8+ T cells. Unlike CXCR5+ CD4+ T cells, when incubated with naive CD19+CD27- B cells, CXCR5+ CD8+ T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5+ CD8+ T cells in B cell-CXCR5+ CD4+ T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5+ CD8+ T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5+ CD8+ T cells tended to associate with low HBV DNA load, and the frequency of CXCR5+ CD8+ T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5+ CD8+ T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.

Keywords: CXCR5+ CD8+ T cell; chronic hepatitis B.

MeSH terms

  • Alanine Transaminase / analysis
  • B-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / virology
  • Coculture Techniques
  • Cytokines / metabolism
  • Female
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver Neoplasms / immunology
  • Liver Neoplasms / virology
  • Male
  • Receptors, CXCR5 / analysis*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Viral Load

Substances

  • CXCR5 protein, human
  • Cytokines
  • Receptors, CXCR5
  • Alanine Transaminase