Dominant transplantation tolerance impairs CD8+ T cell function but not expansion

Alloreactive CD8(+) T cells may persist in animals made tolerant of transplanted tissues; their function is controlled through continuous censorship by regulatory CD4(+) T cells. We sought to establish the stage at which such censorship operates. We found that monospecific CD8(+) T cells introduced into tolerant animals responded to the tolerated tissue antigen as if they had received CD4(+) T cell "help": they proliferated and accumulated normally. However, they did show compromised graft rejection, interferon-gamma production and cell-mediated cytotoxicity. These findings suggest that tolerance mediated by regulatory T cells acts by censoring immune effector functions rather than by limiting the induction of T cell responses.