Alloantigen-specific regulation of cytotoxic T cell responses is mediated through the induction of clonal anergy of CD8+ T cells.

Priming mice with an alloantigen before immunization with this same alloantigen presented in association with a second one on an F1 stimulator cell inhibits the induction of cytotoxic response directed against the second alloantigen. This inhibition is associated with the induction of a strong cytotoxic T lymphocyte (CTL) response against the first priming alloantigen. For example, a specific suppression of anti-H-2b CTL responses could be induced in C3H/He mice (H-2k) by priming them with H-2d spleen cells before immunization with F1 (H-2dxb) spleen cells. In the present study, we have analyzed the mechanisms underlying this specific suppression of CTL responses. We have demonstrated that the reduction of H-2b-specific CTL responses is reflected by a decrease in the frequency of effector cells specific for H-2b antigen. However, there was no difference in the frequencies of precursor CTL in control and suppressed mice excluding clonal deletion as the mechanism maintaining low responsiveness. Co-culture experiments have shown that the suppression of anti-H-2b CTL responses was not due to suppressor cells but to the failure of CD8+ T cells of suppressed mice to collaborate with normal helper CD4+ T cells. The suppression was therefore ascribed to a functional impairment (clonal anergy) of the CD8+ T cell subset.