High frequency of circulating HBcAg-specific CD8 T cells in hepatitis B infection: a flow cytometric analysis

Abstract

SUMMARYViral antigen-specific T cells are important for virus elimination. We studied the hepatitis B virus (HBV)-specific T cell response using flow cytometry. Three phases of HBV infection were studied: Group A, HBeAg (1) chronic hepatitis; Group B, HBeAb (1) HBV carrier after seroconversion; and Group C, HBsAb (1) phase. Peripheral T cells were incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analysed by flow cytometry. HBcAg-specific CD4 and CD8 T cells were identified in all three groups and the number of IFN-g-positive T cells was greater than TNF-a -positive T cells. The frequency of IFN-g-positive CD4 and CD8 T cells was highest in Group C, compared with Groups A and B. No significant difference in the HBcAg-specific T cell response was observed between Group A and Group B. The HBcAg-specific CD8 T cell response was diminished by CD4 depletion, addition of antibody against human leucocyte antigen (HLA) class I, class II or CD40L. Cytokine-positive CD8 T cells without HBcAg stimulation were present at a high frequency (7 of 13 cases) in Group B, but were rare in other groups. HBcAg-specific T cells can be detected at high frequency by a sensitive flow cytometric analysis, and these cells are important for controlling HBV replication.

In Vitro Human Memory CD8 T Cell Expansion in Response to Cytomegalovirus Requires CD4+T Cell Help

“…However, in contrast to observations in murine systems, we found that this expansion was critically dependent on the presence of CD4 + T cells. Likewise, MHC-I-restricted CD8 + T cell proliferation responses to inactivated hepatitis B virus (HBV) Ags also were diminished by CD4 + T cell depletion [31], and, more recently, "effector" CD8 T cell expansion in response to HCMV was shown to be CD4 + T cell dependent [32]. We do not know whether CD4 + T cell help is required for cross-presentation in our system, but CD4 + T cells and/or IL-2 are required for memory CD8 + T cell expansion in response to whole HCMV ( figure 3 and figure 5A), and CD8 + T cell proliferation in response to the NLV9 HCMV peptide is minimal in the presence or absence of CD4 + T cells ( figure 4B and figure 5B).…”

Frequencies of epitope-specific cytotoxic T lymphocytes in active chronic viral hepatitis B infection by using MHC class I peptide tetramers

“…Previous studies have suggested that some HBV-specific CD8+T-cell responses exist in chronic hepatitis [4][5][6], and their contribution was the control of the virus infection, which remained an important unresolved question.…”

Reduced Hepatitis B Virus (HBV)-Specific CD4+T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

“…Examination of HBV-specific T cells by limiting-dilution assays (7,56), proliferation assays (13,29,30,35), tetramer staining (46,58,69), and cytokine production has been limited to responses against predicted HLA-A2 epitopes of core, surface, and polymerase proteins and/or whole-antigen stimulation (2,46,49,64). In HIV-1 infection the dominant HIV-1-specific T-cell response is often to non-HLA-A2-associated peptides as well as to accessory proteins.…”