期刊
NATURE IMMUNOLOGY
卷 20, 期 7, 页码 890-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-019-0403-4
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- G. Gutierrez-Cruz (National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS))
- NHGRI, National Institute of Allergy and Infectious Diseases, NIAMS
- National Institute of Neurological Disorders and Stroke
- National Cancer Institute, National Institutes of Health (NIH)
- NIH [AG056524]
- University of Pennsylvania cancer immunotherapy program
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZICHG200350] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI001240] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [ZIHAR041173, ZIAAR041159] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS003111] Funding Source: NIH RePORTER
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(+) Tcells 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.
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