TY - JOUR
T1 - IL-27 promotes the expansion of self-renewing CD8+ T cells in persistent viral infection
AU - Huang, Zhe
AU - Zak, Jaroslav
AU - Pratumchai, Isaraphorn
AU - Shaabani, Namir
AU - Vartabedian, Vincent F.
AU - Nguyen, Nhan
AU - Wu, Tuoqi
AU - Xiao, Changchun
AU - Teijaro, John R.
N1 - Publisher Copyright:
© 2019 Huang et al.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20190173
DO - 10.1084/jem.20190173
M3 - Article
C2 - 31164392
AN - SCOPUS:85071063566
SN - 0022-1007
VL - 216
SP - 1791
EP - 1808
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -