Research ArticleT CELLS

TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells

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Science Immunology  03 Jul 2020:
Vol. 5, Issue 49, eaba7918
DOI: 10.1126/sciimmunol.aba7918

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The TOX profiles of T cells

Transcription factors TOX and TCF-1 have emerged as key drivers of exhaustion and stemness programs in CD8+ T cells. Using bulk and single-cell transcriptome analyses and flow cytometric analyses, Sekine et al. have generated a detailed map of TOX and TCF-1 expression in human CD8+ T cells. TOX is generally expressed by effector memory CD8+ T cells and is not restricted to exhausted T cells, whereas TCF-1 demarcates early-differentiated, memory CD8+ T cells. Using tetramers to examine the specificity of antigen-specific CD8+ T cells, they found that cytotoxic memory CD8+ T cells targeting both pathogenic and well-controlled chronic infections are more likely to express TOX. Their results propose that TOX-dependent transcriptional wiring is not restricted to exhausted CD8+ T cells.

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