Functional modulation of hepatitis B core antigen-specific T lymphocytes by an autoreactive T cell clone.
Hepatitis B core (HBc)Ag-specific T cells present in the peripheral blood of a patient with chronic active hepatitis B were expanded by co-cultivation for 7 days with rHBcAg. After cloning at 1 cell/well in the presence of PHA and IL-2, five HBcAg-specific CD4+ cloned lines were obtained. All five lines proliferated and produced IL-2, IFN-gamma, and TNF in a dose-dependent fashion in response to HBcAg, but not to HBV envelope Ag. The cloned lines and derivative clones were HLA class II (DR1) restricted. All T cell clones were able to induce anti-HBc production by autologous B cells in response to HBcAg (helper effect). The proliferative response and the helper effect of the HBcAg-specific T cell lines and clones were augmented by co-cultivation with an autologous, autoreactive (HLA-DQ1 specific) T cell clone, even in the absence of HBcAg, and the autoreactive T cells directly stimulated anti-HBc secretion by autologous B cells, presumably due to the release of Ag-nonspecific factors. These findings define a model immunoregulatory circuit the physiologic significance of which remains to be determined.
Ferrari
C
C
Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Chisari
F V
FV
Ribera
E
E
Penna
A
A
Mondelli
M U
MU
D000328:Adult; D002450:Cell Communication; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000378:metabolism; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006521:Hepatitis, Chronic / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
D000939:Epitopes; D006512:Hepatitis B Core Antigens; D008222:Lymphokines