RT Journal Article
SR Electronic
T1 Regulatory T cells suppress the formation of super-effector CD8 T cells by limiting IL-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.10.467495
DO 10.1101/2021.11.10.467495
A1 Oksana Tsyklauri
A1 Tereza Chadimova
A1 Veronika Niederlova
A1 Jirina Kovarova
A1 Juraj Michalik
A1 Iva Malatova
A1 Sarka Janusova
A1 Helene Rossez
A1 Ales Drobek
A1 Hana Vecerova
A1 Virginie Galati
A1 Marek Kovar
A1 Ondrej Stepanek
YR 2021
UL http://biorxiv.org/content/early/2021/11/12/2021.11.10.467495.abstract
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.