Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection

Yao C, Sun HW, Lacey NE, Ji Y, Moseman EA, Shih HY, Heuston EF, Kirby M, Anderson S, Cheng J, Khan O, Handon R, Reilley J, Fioravanti J, Hu J, Gossa S, Wherry EJ, Gattinoni L, Mcgavern DB, O'Shea JJ, Schwartzberg PL, Wu T (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Immunology Nature Research

Book Volume: 20

Pages Range: 890-901

Journal Issue: 7

DOI: 10.1038/s41590-019-0403-4

Abstract

Progenitor-like CD8+ T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct programs to adapt to the immunosuppressive environment. By comparing the single-cell transcriptomes and epigenetic profiles of CD8+ T cells responding to acute and chronic viral infections, we found that progenitor-like CD8+ T cells became distinct from memory precursor cells before the peak of the T cell response. We discovered a coexpression gene module containing Tox that exhibited higher transcriptional activity associated with more abundant active histone marks in progenitor-like cells than memory precursor cells. Moreover, thymocyte selection-associated high mobility group box protein TOX (TOX) promoted the persistence of antiviral CD8+ T cells and was required for the programming of progenitor-like CD8+ T cells. Thus, long-term CD8+ T cell immunity to chronic viral infection requires unique transcriptional and epigenetic programs associated with the transcription factor TOX.

Involved external institutions

US National Institutes of Health (NIH) US United States (USA) (US) National Human Genome Research Institute (NHGRI) US United States (USA) (US) University of Pennsylvania US United States (USA) (US) National Cancer Institute (NCI) US United States (USA) (US) National Institute of Neurological Disorders and Stroke (NINDS) US United States (USA) (US)

How to cite

APA:

Yao, C., Sun, H.-W., Lacey, N.E., Ji, Y., Moseman, E.A., Shih, H.-Y.,... Wu, T. (2019). Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection. Nature Immunology, 20(7), 890-901. https://doi.org/10.1038/s41590-019-0403-4

MLA:

Yao, Chen, et al. "Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection." Nature Immunology 20.7 (2019): 890-901.

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