The suppression of delayed‐type hypersensitivity by CD8+ regulatory T cells requires interferon‐γ

Summary CD8+ regulatory (suppressor) T cells are induced by complex cellular pathways in the spleens of mice that have received an injection of antigen into the anterior chamber (AC) of an eye, an immune‐privileged site. Although these CD8+ regulatory T cells perform an antigen‐specific regulatory function for an immune response to self and non‐self antigens, the mechanisms of the activation or function of these regulatory cells are not clear. Here, we describe a novel mechanism for the activation of splenic CD8+ regulatory T cells induced by injection of antigen into the AC. Immunization of mice with trinitrophenyl and bovine serum albumin (TNP‐BSA) amplified AC‐induced splenic CD8+ regulatory T cells that suppressed the initiation of contact sensitivity when transferred to immunized, challenged mice. These CD8+ regulatory T cells were produced independently of perforin, indicating that they are not canonical cytotoxic T cells. Fas ligand (FasL)‐deficient CD8+ regulatory T‐cell function was rescued by inclusion of exogenous interferon‐γ (IFN‐γ), demonstrating that the expression of FasL by CD8+ regulatory T cells was dispensable, but IFN‐γ was not. Ultimately, we demonstrated that the generation of these CD8+ regulatory T cells occurred independently of IFN‐γ, but their suppressor function required IFN‐γ receptor stimulation.