PT  - JOURNAL ARTICLE
AU  - Oksana Tsyklauri
AU  - Tereza Chadimova
AU  - Veronika Niederlova
AU  - Jirina Kovarova
AU  - Juraj Michalik
AU  - Iva Malatova
AU  - Sarka Janusova
AU  - Helene Rossez
AU  - Ales Drobek
AU  - Hana Vecerova
AU  - Virginie Galati
AU  - Marek Kovar
AU  - Ondrej Stepanek
TI  - Regulatory T cells suppress the formation of super-effector CD8 T cells by limiting IL-2
AID  - 10.1101/2021.11.10.467495
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.11.10.467495
4099  - http://biorxiv.org/content/early/2021/11/12/2021.11.10.467495.short
4100  - http://biorxiv.org/content/early/2021/11/12/2021.11.10.467495.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.