Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions

Transcription factors ThPOK and Runx3 regulate the differentiation of "helper" CD4+ and "cytotoxic" CD8+ T cell lineages respectively, inducing single positive (SP) T cells that enter the periphery with the expression of either the CD4 or CD8 co-receptor. Despite the expectation...

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Vydáno v:	The Journal of experimental medicine Ročník 219; číslo 6
Hlavní autoři:	Schad, Sara E, Chow, Andrew, Mangarin, Levi, Pan, Heng, Zhang, Jiajia, Ceglia, Nicholas, Caushi, Justina X, Malandro, Nicole, Zappasodi, Roberta, Gigoux, Mathieu, Hirschhorn, Daniel, Budhu, Sadna, Amisaki, Masataka, Arniella, Monica, Redmond, David, Chaft, Jamie, Forde, Patrick M, Gainor, Justin F, Hellmann, Matthew D, Balachandran, Vinod, Shah, Sohrab, Smith, Kellie N, Pardoll, Drew, Elemento, Olivier, Wolchok, Jedd D, Merghoub, Taha
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 06.06.2022
Témata:	Animals CD4 Antigens - metabolism CD4-Positive T-Lymphocytes CD8 Antigens - metabolism CD8-Positive T-Lymphocytes Cell Differentiation Cell Lineage - genetics Melanoma - metabolism Mice T-Lymphocyte Subsets
ISSN:	1540-9538, 1540-9538
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Popis
Shrnutí:	Transcription factors ThPOK and Runx3 regulate the differentiation of "helper" CD4+ and "cytotoxic" CD8+ T cell lineages respectively, inducing single positive (SP) T cells that enter the periphery with the expression of either the CD4 or CD8 co-receptor. Despite the expectation that these cell fates are mutually exclusive and that mature CD4+CD8+ double positive (DP) T cells are present in healthy individuals and augmented in the context of disease, yet their molecular features and pathophysiologic role are disputed. Here, we show DP T cells in murine and human tumors as a heterogenous population originating from SP T cells which re-express the opposite co-receptor and acquire features of the opposite cell type's phenotype and function following TCR stimulation. We identified distinct clonally expanded DP T cells in human melanoma and lung cancer by scRNA sequencing and demonstrated their tumor reactivity in cytotoxicity assays. Our findings indicate that antigen stimulation induces SP T cells to differentiate into DP T cell subsets gaining in polyfunctional characteristics.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1540-9538 1540-9538
DOI:	10.1084/jem.20212169