Characterization of T-cell tolerance to hepatitis B virus (HBV) antigen in transgenic mice.
We made three different lines of hepatitis B virus (HBV) transgenic mice which express different amounts of hepatitis B e antigen (HBeAg) and/or hepatitis B core antigen (HBcAg) to analyse the cellular mechanisms of HBcAg specific T-cell tolerance. BS10 (official designation, 1.2HB-BS10) transgenic mice, which contain the whole HBV genome, express relatively high amounts of HBeAg in the serum and HBcAg in the liver. SPC mice, which contain hepatitis B virus core and precore gene, express small amounts of HBeAg in the serum but not HBcAg in the liver. SC33 mice, which contain only hepatitis B core gene, do not express HBeAg in the serum but express HBcAg in the liver. BS10 mice showed a very low anti-HBc antibody response after primary and secondary immunizations with recombinant HBcAg compared to transgenic host C57BL/6 (B6) mice. SPC mice showed an almost equal level of anti-HBc antibody response compared to B6 mice. SC33 mice contained anti-HBc antibody even before immunization and showed high titres of anti-HBc antibody response after immunization with HBcAg. Analysis of cellular site(s) of low responsiveness of BS10 mice revealed that proliferating and helper T cells are specifically tolerant to HBcAg. B cells and antigen-presenting cells in BS10 mice were not defective. SC33, SPC and BS10 mice differ a little in their developmental expression of HBc/HBeAg. Our results suggest critical roles of the nature (circulating versus non-circulating) as well as the time of expression of self-antigens in T-cell tolerance.
Takashima
H
H
Department of Immunology, Saga Medical School, Japan.
Araki
K
K
Miyazaki
J
J
Yamamura
K
K
Kimoto
M
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006512:Hepatitis B Core Antigens / Q000032:analysis / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000032:analysis; D007108:Immune Tolerance / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens