T cell Ig mucin (Tim) molecules modulate CD4⁺ T cell responses. In keeping with the view that Tim-1 generates a stimulatory signal for CD4⁺ T cell activation, we hypothesized that an agonist Tim-1–specific mAb would intensify the CD4⁺ T cell–dependant allograft response. Unexpectedly, we determined that a particular Tim-1–specific mAb exerted reciprocal effects upon the commitment of alloactivated T cells to regulatory and effector phenotypes. Commitment to the Th1 and Th17 phenotypes was fostered, whereas commitment to the Treg phenotype was hindered. Moreover, ligation of Tim-1 in vitro effectively deprogrammed Tregs and thus produced Tregs unable to control T cell responses. Overall, the effects of the agonist Tim-1–specific mAb on the allograft response stemmed from enhanced expansion and survival of T effector cells; a capacity to deprogram natural Tregs; and inhibition of the conversion of naive CD4⁺ T cells into Tregs. The reciprocal effects of agonist Tim-1–specific mAbs upon effector T cells and Tregs serve to prevent allogeneic transplant tolerance.