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

Yao, Chen; Sun, Hong-Wei; Lacey, Neal E; Ji, Yun; Moseman, E Ashley; Shih, Han-Yu; Heuston, Elisabeth F; Kirby, Martha; Anderson, Stacie; Cheng, Jun; Khan, Omar; Handon, Robin; Reilley, Julie; Fioravanti, Jessica; Hu, Jinhui; Gossa, Selamawit; Wherry, E John; Gattinoni, Luca; McGavern, Dorian B; O'Shea, John J; Schwartzberg, Pamela L; Wu, Tuoqi.
Nat Immunol; 20(7): 890-901, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209400
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.
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