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STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles


A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1(hi), but compared to their CD57- PD-1(hi) counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57- PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1(hi) cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.

Type Journal
ISBN 2045-2322 (Electronic) 2045-2322 (Linking)
Authors Alshekaili, J.; Chand, R.; Lee, C. E.; Corley, S.; Kwong, K.; Papa, I.; Fulcher, D. A.; Randall, K. L.; Leiding, J. W.; Ma, C. S.; Wilkins, M. R.; Uzel, G.; Goodnow, C. C.; Vinuesa, C. G.; Tangye, S. G.; Cook, M. C.
Responsible Garvan Author Prof Stuart Tangye
Publisher Name Scientific Reports
Published Date 2018-02-23
Published Volume 8
Published Issue 1
Published Pages 3529
Status Always Electronic
DOI 10.1038/s41598-018-21389-8
URL link to publisher's version