CD8⁺CD122⁺ regulatory T cells recognize activated T cells via conventional MHC class I - αβTCR interaction and become IL-10-producing active regulatory cells

CD8⁺CD122⁺ regulatory T cells (CD8⁺ CD122⁺ Treg) are naturally occurring Treg that effectively suppress the proliferation and IFN-γ production of both CD8⁺ and CD4⁺ target cells. This study investigated the molecular mechanisms of the recognition of target cells by CD8⁺CD122⁺ Treg using an in vitro culture system that reconstitutes the regulatory action of these cells. Naive CD8⁺CD122⁺ Treg co-cultured with pre-activated T cells became active Treg that produced IL-10 and suppressed IFN-γ production from the target T cells. CD8⁺CD122⁺ Treg effectively suppressed the IFN-γ production of the target cells of syngeneic mouse strains but not of allogeneic mouse strains with incompatible MHC. By using MHC-congeneic mouse strains, MHC-restricted suppression by CD8⁺CD122⁺ Treg was further confirmed. The blockade of cell surface molecules either on the Treg or on the target cells by specific blocking antibodies indicated that H-2K, H-2D, αβTCR and CD8 were involved in the regulatory action but I-A and Qa-1 were not. These results indicate that CD8⁺CD122⁺ Treg recognize already-activated T cells via the interaction of conventional MHC class I - αβTCR and become active regulatory cells that produce IL-10 and suppress the target cells.