MHC-restricted minimal regulatory circuit initiated by a class II-autoreactive T cell clone.
The in vivo administration of a self-class II-reactive Th clone MS202 derived from C3H into syngeneic mice resulted in the suppression of both primary and early secondary antibody responses against T cell-dependent antigens. The suppression was due to the generation of antigen-nonspecific Ts cells in the recipient, as the splenic T cells from the mice treated with MS202 were able to strongly suppress the in vitro secondary antibody response of primed syngeneic spleen cells. The dose-response curve of suppression indicated the generation of an effector type Ts that directly suppressed Th. The surface phenotype of Ts was Ly-1+,2-, L3T4+, I-J-. The presence of Ly-1+,2+ T cells was not required to induce the suppression. The suppression was strictly restricted to H-2k, as F1 Ts cells were able to suppress the response of C3H but not of B6 B cells helped by the same F1 Th cells. The experiments with chimeric mice indicated that the direct target of Ts is an MHC-restricted Th but not a B cell or APC. The results indicate the existence of a minimal regulatory circuit where an MHC-restricted Th induces a preprogrammed Ts that in turn directly suppresses Th with the same MHC-restriction specificity. The induction of and suppression by Ts appeared to be due to the direct recognition of MHC restriction sites of Th cells.
D000818:Animals; D000917:Antibody Formation; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D007108:Immune Tolerance; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology