Regulatory T cells (Tregs) are indispensable for maintaining self-tolerance by suppressing conventional T cells. On the other hand, Tregs may promote tumor growth by inhibiting anti-cancer immunity. In this study, we identified that Tregs increase the quorum of self-reactive CD8+ T cells required for the induction of experimental autoimmune diabetes. Their major suppression mechanism is limiting available IL-2, a key cytokine for activated T cells. Specifically, Tregs inhibit the formation of a previously uncharacterized subset of antigen-stimulated CD8+ T cells. Since these T cells express high levels of IL-7 receptor and cytotoxic molecules (KLRK1, GZMB), and show superior cell killing abilities, we call them super-effector T cells. The administration of agonistic IL-2 immunocomplexes phenocopies the absence of Tregs, i.e., it induces super-effector T cells, promotes autoimmunity, and enhances anti-tumor responses. Counterparts of super-effector T cells were found in the human blood, revealing them as a potential target for immunotherapy.
Nanoparticles Containing an Insulin–ChgA Hybrid Peptide Protect from Transfer of Autoimmune Diabetes by Shifting the Balance between Effector T Cells and Regulatory T Cells