The TOX profiles of T cells

Abstract

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. 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, the authors found that cytotoxic memory CD8+ T cells targeting both pathogenic and well-controlled chronic infections are more likely to express TOX. These results support a model in which TOX-dependent transcriptional wiring is not restricted to exhausted CD8+ T cells. Sci. Immunol. 5 , eaba7918 (2020).