1. The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1 + CD8 + T cells in chronic viral infection.
- Author
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Marx AF, Kallert SM, Brunner TM, Villegas JA, Geier F, Fixemer J, Abreu-Mota T, Reuther P, Bonilla WV, Fadejeva J, Kreutzfeldt M, Wagner I, Aparicio-Domingo P, Scarpellino L, Charmoy M, Utzschneider DT, Hagedorn C, Lu M, Cornille K, Stauffer K, Kreppel F, Merkler D, Zehn D, Held W, Luther SA, Löhning M, and Pinschewer DD
- Subjects
- Animals, Mice, Alarmins metabolism, Interleukin-1 Receptor-Like 1 Protein metabolism, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Persistent Infection, T Cell Transcription Factor 1 metabolism, CD8-Positive T-Lymphocytes, Interleukin-33 metabolism, Lymphocytic Choriomeningitis immunology
- Abstract
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., Competing Interests: Declaration of interests D.D.P. is a founder, consultant, and shareholder of Hookipa Pharma Inc. commercializing arenavirus-based vector technology, and he as well as W.V.B., S.M.K., and D.M. are listed as inventor on corresponding patents., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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