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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00569557" target="_blank" >RIV/68378050:_____/23:00569557 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/23:00569557 RIV/00216208:11310/23:10479727

Výsledek na webu

<a href="https://elifesciences.org/articles/79342" target="_blank" >https://elifesciences.org/articles/79342</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.79342" target="_blank" >10.7554/eLife.79342</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

eLife

ISSN

2050-084X

e-ISSN

2050-084X

Svazek periodika

12

Číslo periodika v rámci svazku

Jan 27

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

30

Strana od-do

e79342

Kód UT WoS článku

000941583600001

EID výsledku v databázi Scopus

2-s2.0-85147108371