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

Jalila Alshekaili, Rochna Chand, Cindy Eunhee Lee, Susan Corley, Kristy Kwong, Ilenia Papa, David A. Fulcher, Katrina L. Randall, Jennifer W. Leiding, Cindy S. Ma, Marc R. Wilkins, Gulbu Uzel, Chris C. Goodnow, Carola G. Vinuesa, Stuart G. Tangye, Matthew C. Cook

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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-1hi, but compared to their CD57-PD-1hi 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-1hi 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.

Original languageEnglish
Article number3529
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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T-Lymphocytes
Cytokines
Phenotype
Germinal Center
Helper-Inducer T-Lymphocytes
Interleukin-10
Mutation
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles. / Alshekaili, Jalila; Chand, Rochna; Lee, Cindy Eunhee; Corley, Susan; Kwong, Kristy; Papa, Ilenia; Fulcher, David A.; Randall, Katrina L.; Leiding, Jennifer W.; Ma, Cindy S.; Wilkins, Marc R.; Uzel, Gulbu; Goodnow, Chris C.; Vinuesa, Carola G.; Tangye, Stuart G.; Cook, Matthew C.

In: Scientific Reports, Vol. 8, No. 1, 3529, 01.12.2018.

Research output: Contribution to journalArticle

Alshekaili, J, Chand, R, Lee, CE, Corley, S, Kwong, K, Papa, I, Fulcher, DA, Randall, KL, Leiding, JW, Ma, CS, Wilkins, MR, Uzel, G, Goodnow, CC, Vinuesa, CG, Tangye, SG & Cook, MC 2018, 'STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles', Scientific Reports, vol. 8, no. 1, 3529. https://doi.org/10.1038/s41598-018-21389-8
Alshekaili, Jalila ; Chand, Rochna ; Lee, Cindy Eunhee ; Corley, Susan ; Kwong, Kristy ; Papa, Ilenia ; Fulcher, David A. ; Randall, Katrina L. ; Leiding, Jennifer W. ; Ma, Cindy S. ; Wilkins, Marc R. ; Uzel, Gulbu ; Goodnow, Chris C. ; Vinuesa, Carola G. ; Tangye, Stuart G. ; Cook, Matthew C. / STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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abstract = "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-1hi, but compared to their CD57-PD-1hi 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-1hi 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.",
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AU - Fulcher, David A.

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AU - Wilkins, Marc R.

AU - Uzel, Gulbu

AU - Goodnow, Chris C.

AU - Vinuesa, Carola G.

AU - Tangye, Stuart G.

AU - Cook, Matthew C.

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