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Regulatory T cells suppress the formation of potent KLRK1 and IL- 7R expressing effector CD8 T cells by limiting IL-2
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SYSNO ASEP 0569557 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Regulatory T cells suppress the formation of potent KLRK1 and IL- 7R expressing effector CD8 T cells by limiting IL-2 Author(s) Tsyklauri, Oksana (UMG-J)
Chadimová, Tereza (UMG-J)
Niederlová, Veronika (UMG-J) ORCID
Kovářová, Jiřina (MBU-M)
Michálik, Juraj (UMG-J) ORCID
Malátová, Iva (MBU-M)
Janušová, Šárka (UMG-J) ORCID
Ivashchenko, Olha (UMG-J) ORCID
Rossez, H. (CH)
Drobek, Aleš (UMG-J) ORCID
Večeřová, Hana (UMG-J)
Galati, V. (CH)
Kovář, Marek (MBU-M) RID, ORCID
Štěpánek, Ondřej (UMG-J) RID, ORCIDArticle number e79342 Source Title eLife. - : eLife - ISSN 2050-084X
Roč. 12, Jan 27 (2023)Number of pages 30 s. Language eng - English Country GB - United Kingdom Keywords IL-2 ; T cells ; autoimmunity ; cytotoxic ; immune suppression ; immunology ; inflammation ; mouse ; regulatory T cells OECD category Immunology R&D Projects LX22NPO5103 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LX22NPO5102 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GJ19-03435Y GA ČR - Czech Science Foundation (CSF) GA22-20548S GA ČR - Czech Science Foundation (CSF) GA22-18046S GA ČR - Czech Science Foundation (CSF) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 ; MBU-M - RVO:61388971 UT WOS 000941583600001 EID SCOPUS 85147108371 DOI 10.7554/eLife.79342 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2024 Electronic address https://elifesciences.org/articles/79342
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