Regulatory T Cells Suppress the Formation of Potent KLRK1 and IL-7R Expressing Effector CD8 T Cells by Limiting IL-2

Overview

Journal Elife

Specialty Biology

Date 2023 Jan 27

PMID 36705564

Authors

Oksana Tsyklauri

Tereza Chadimova

Veronika Niederlova

Jirina Kovarova

Juraj Michalik

Iva Malatova

Sarka Janusova

Olha Ivashchenko

Helene Rossez

Ales Drobek

Hana Vecerova

Virginie Galati

Marek Kovar

Ondrej Stepanek

Affiliations

Soon will be listed here.

Abstract

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.

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