Regulatory T cells suppress the formation of potent KLRK1 and IL- 7R expressing effector CD8 T cells by limiting IL-2

0569557 - ÚMG 2024 RIV GB eng J - Článek v odborném periodiku
Tsyklauri, Oksana - Chadimová, Tereza - Niederlová, Veronika - Kovářová, Jiřina - Michálik, Juraj - Malátová, Iva - Janušová, Šárka - Ivashchenko, Olha - Rossez, H. - Drobek, Aleš - Večeřová, Hana - Galati, V. - Kovář, Marek - Štěpánek, Ondřej
Regulatory T cells suppress the formation of potent KLRK1 and IL- 7R expressing effector CD8 T cells by limiting IL-2.
eLife. Roč. 12, Jan 27 (2023), č. článku e79342. ISSN 2050-084X. E-ISSN 2050-084X
Grant CEP: GA MŠMT(CZ) LX22NPO5103; GA MŠMT LX22NPO5102; GA ČR GJ19-03435Y; GA ČR(CZ) GA22-20548S; GA ČR GA22-18046S; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2018126; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109
GRANT EU: European Commission(XE) 802878 - FunDiT
Institucionální podpora: RVO:68378050 ; RVO:61388971
Klíčová slova: IL-2 * T cells * autoimmunity * cytotoxic * immune suppression * immunology * inflammation * mouse * regulatory T cells
Obor OECD: Immunology; Immunology (MBU-M)
Impakt faktor: 7.7, rok: 2022
Způsob publikování: Open access
https://elifesciences.org/articles/79342

Regulatory T cells (Tregs) are indispensable for maintaining self-tolerance by suppressing conventional T cells. On the other hand, Tregs promote tumor growth by inhibiting anticancer 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 in mice. Their major suppression mechanism is limiting available IL-2, an essential T-cell cytokine. Specifically, Tregs inhibit the formation of a previously uncharacterized subset of antigen-stimulated KLRK1+ IL-7R+ (KILR) CD8+ effector T cells, which are distinct from conventional effector CD8+ T cells. KILR CD8+ T cells show superior cell-killing abilities in vivo. The administration of agonistic IL-2 immunocomplexes phenocopies the absence of Tregs, i.e., it induces KILR CD8+ T cells, promotes autoimmunity, and enhances antitumor responses in mice. Counterparts of KILR CD8+ T cells were found in the human blood, revealing them as a potential target for immunotherapy.
Trvalý link: https://hdl.handle.net/11104/0340929