CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-alphabetaTCR 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-gamma 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-gamma production from the target T cells. CD8(+)CD122(+) Treg effectively suppressed the IFN-gamma 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, alphabetaTCR 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-alphabetaTCR and become active regulatory cells that produce IL-10 and suppress the target cells.