The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8+ T cells in chronic viral infection
Authors:
- Marx, Anna-Friederike
- Kallert, Sandra M.
- Brunner, Tobias M.
- Villegas, José A.
- Geier, Florian
- Fixemer, Jonas
- Abreu-Mota, Tiago
- Reuther, Peter
- Bonilla, Weldy V.
- Fadejeva, Jelizaveta
- Kreutzfeldt, Mario
- Wagner, Ingrid
- Aparicio-Domingo, Patricia
- Scarpellino, Leo
- Charmoy, Mélanie
- Utzschneider, Daniel T.
- Hagedorn, Claudia
- Lu, Min
- Cornille, Karen
- Stauffer, Karsten
- Kreppel, Florian
- Merkler, Doron
- Zehn, Dietmar
- Held, Werner
- Luther, Sanjiv A.
- Löhning, Max
- Pinschewer, Daniel D.
Details:
Immunity, Volume 56, Issue 4, 2023-04-11
Article Link: Click here
T cell factor 1 (Tcf-1) expressing CD8+ T cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these stem-like CD8+ T cells (CD8+SL) remain poorly defined. Studying CD8+ T cell differentiation in mice with chronic viral infection, we identified the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8+SL as well as for virus control. IL-33 receptor (ST2)-deficient CD8+ T cells exhibited biased end differentiation and premature loss of Tcf-1. ST2-deficient CD8+SL responses were restored by blockade of type I interferon signaling, suggesting that IL-33 balances IFN-I effects to control CD8+SL formation in chronic infection. IL-33 signals broadly augmented chromatin accessibility in CD8+SL and determined these cells’ re-expansion potential. Our study identifies the IL-33-ST2 axis as an important CD8+SL-promoting pathway in the context of chronic viral infection.