IL-27 promotes the expansion of self-renewing CD8+ T cells in persistent viral infection

Zhe Huang, Jaroslav Zak, Isaraphorn Pratumchai, Namir Shaabani, Vincent F. Vartabedian, Nhan Nguyen, Tuoqi Wu, Changchun Xiao, John R. Teijaro

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5+ TCF1+ CD8+ T cells that sustain T cell responses during persistent infection and proliferate upon anti-PD1 treatment. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to CXCR5+ CD8+ T cell expansion in an IL-27– and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8+ T cells. We found that CD8+ T cell–intrinsic IL-27 signaling safeguards the ability of TCF1hi cells to maintain proliferation and avoid terminal differentiation or programmed cell death. Mechanistically, IL-27 endowed rapidly dividing cells with IRF1, a transcription factor that was required for sustained division in a cell-intrinsic manner. These findings reveal that IL-27 opposes IFN-I to uncouple effector differentiation from cell division and suggest that IL-27 signaling could be exploited to augment self-renewing T cells in chronic infections and cancer.

Original languageEnglish (US)
Pages (from-to)1791-1808
Number of pages18
JournalJournal of Experimental Medicine
Volume216
Issue number8
DOIs
StatePublished - Aug 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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