STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles.
Sci Rep
; 8(1): 3529, 2018 02 23.
Article
in En
| MEDLINE
| ID: mdl-29476109
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes, Cytotoxic
/
Tonsillitis
/
Gene Expression Regulation
/
T-Lymphocytes, Helper-Inducer
/
CD57 Antigens
/
STAT3 Transcription Factor
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Sci Rep
Year:
2018
Type:
Article
Affiliation country:
Australia