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 (HBeAg)-specific CD4(+) T-cell respons es are believed to play an important role in the control of human HBV infec tion. 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 HBcA g-specific CD4(+) Th1-type T cells were able to lyse HBc peptide-loaded Eps tein-Barr virus-transformed lymphoblastoid target cells in vitro. To examin e whether these HLA-DR13*- restricted human CD4(+) Th1 T cells also display the same cytotoxic effects in vivo, we transferred peripheral blood leukoc ytes (PBL) derived from HBV-infected donors or an HBV-naive donor sharing t he DR13*, together with the HBcAg-specific CD4(+) Th1-type T cells and HBcA g, directly into the spleen of optimally conditioned Nod/LtSz-Prkdc(scid)/P rkdc(scid) (NOD/SCID) mice. The production of both secondary anti-HBc-immun oglobulin 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 shar e an HLA-DR13. These results suggest that HBeAg-specific CD4(+) Th1 T cells may be able to lyse HBcAg-binding, or -specific, B cells that have taken u p and presented HBcAg in a class II-restricted manner. Thus, HBeAg-specific CD4(+) Th1-type T cells can modulate the function and exert a regulatory r ole in deleting HBcAg-binding, or -specific, human B cells in vivo, which m ay be of importance in controlling the infection.