In vivo inhibition of anti-hepatitis B virus core antigen (HBcAg) immunoglobulin G production by HBcAg-specific CD4(+) Th1-type T-cell clones in a hu-PBL-NOD/SCID mouse model.
Hepatitis B virus (HBV) core antigen (HBcAg)-specific CD4(+) T-cell responses are believed to play an important role in the control of human HBV infection. In the present study, HBcAg-specific, HLA-DR13*-restricted CD4(+) Th1-type T-cell clones were generated which secreted both gamma interferon and tumor necrosis factor alpha after in vitro antigen stimulation. These HBcAg-specific CD4(+) Th1-type T cells were able to lyse HBc peptide-loaded Epstein-Barr virus-transformed lymphoblastoid target cells in vitro. To examine whether these HLA-DR13*-restricted human CD4(+) Th1 T cells also display the same cytotoxic effects in vivo, we transferred peripheral blood leukocytes (PBL) derived from HBV-infected donors or an HBV-naïve donor sharing the DR13*, together with the HBcAg-specific CD4(+) Th1-type T cells and HBcAg, directly into the spleen of optimally conditioned Nod/LtSz-Prkdc(scid)/Prkdc(scid) (NOD/SCID) mice. The production of both secondary anti-HBc-immunoglobulin G (anti-HBc-IgG) and primary HBcAg-binding IgM in hu-PBL-NOD/SCID mice was drastically inhibited by HBcAg-specific CD4(+) Th1-type T cells. No inhibition was observed when CD4(+) Th1 cells and donor PBL did not share an HLA-DR13. These results suggest that HBcAg-specific CD4(+) Th1 T cells may be able to lyse HBcAg-binding, or -specific, B cells that have taken up and presented HBcAg in a class II-restricted manner. Thus, HBcAg-specific CD4(+) Th1-type T cells can modulate the function and exert a regulatory role in deleting HBcAg-binding, or -specific, human B cells in vivo, which may be of importance in controlling the infection.
Cao
T
T
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Meuleman
P
P
Desombere
I
I
Sällberg
M
M
Leroux-Roels
G
G
D000818:Animals; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006509:Hepatitis B / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008954:Models, Biological; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology*
D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G