The control of CD8+ T cell responses is preserved in perforin-deficient mice and released by depletion of CD4+CD25+ regulatory T cells

Perforin expression in the host is not required for the normal regulation of perforin‐sufficient CD8+ T cell responses after dendritic cell immunization. Immune suppression by Treg has been demonstrated in a number of models, but the mechanisms of this suppression are only partly understood. Recent work has suggested that Tregs may suppress by directly killing immune cell populations in vivo in a perforin‐ and granzyme B‐dependent manner. To establish whether perforin is necessary for the regulation of immune responses in vivo, we examined OVA‐specific CD8+ T cell responses in WT and PKO mice immunized with OVA and α‐GalCer and the expansion of WT OT‐I CD8+ T cells adoptively transferred into WT or PKO mice immunized with DC‐OVA. We observed similar expansion, phenotype, and effector function of CD8+ T cells in WT and PKO mice, suggesting that CD8+ T cells were subjected to a similar amount of regulation in the two mouse strains. In addition, when WT and PKO mice were depleted of Tregs by anti‐CD25 mAb treatment before DC‐OVA immunization, CD8+ T cell proliferation, cytotoxicity, and cytokine production were increased similarly, suggesting a comparable involvement of CD25+ Tregs in controlling T cell proliferation and effector function in these two mouse strains. These data suggest that perforin expression is not required for normal immune regulation in these models of in vivo CD8+ T cell responses induced by immunization with OVA and α‐GalCer or DC‐OVA.