Divergent fates of antigen-specific CD8 + T cell clones in mice with acute leukemia.

Autor: Chen X; Department of Medicine, University of Chicago, Chicago, IL, USA., MacNabb BW; Committee on Immunology, University of Chicago, Chicago, IL, USA., Flood B; Committee on Immunology, University of Chicago, Chicago, IL, USA., Blazar BR; Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA., Kline J; Department of Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA; University of Chicago Comprehensive Cancer Center, Chicago, IL, USA. Electronic address: jkline@medicine.bsd.uchicago.edu.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2021 Nov 09; Vol. 37 (6), pp. 109991.
DOI: 10.1016/j.celrep.2021.109991
Abstrakt: The existence of a dysfunctional CD8 + T cell state in cancer is well established. However, the degree to which CD8 + T cell fates are influenced by the context in which they encounter cognate tumor antigen is less clear. We previously demonstrated that CD8 + T cells reactive to a model leukemia antigen were deleted by antigen cross-presenting type 1 conventional dendritic cells (cDC1s). Here, through a study of T cell receptor (TCR) transgenic CD8 + T cells (TCR Tg101 ) reactive to a native C1498 leukemia cell antigen, we uncover a different mode of T cell tolerance in which TCR Tg101 undergo progressive expansion and differentiation into an exhausted state. Antigen encounter by TCR Tg101 requires leukemia cell major histocompatibility complex (MHC)-I expression and is independent of DCs, implying that leukemia cells directly mediate the exhausted TCR Tg101 phenotype. Collectively, our data reveal that leukemia antigens are presented to CD8 + T cells via discrete pathways, leading to distinct tolerant states.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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