CD4 effector T cell differentiation is controlled by IL-15 that is expressed and presented in trans.
Cytokine
; 99: 266-274, 2017 11.
Article
em En
| MEDLINE
| ID: mdl-28807496
ABSTRACT
T cells are both producers and consumers of cytokines, and autocrine cytokine signaling plays a critical role in T cell immunity. IL-15 is a homeostatic cytokine for T cells that also controls inflammatory immune responses. An autocrine role of T cell-derived IL-15, however, remains unclear. Here we examined IL-15 expression and signaling upon effector T cell differentiation in mice, and, surprisingly, found that CD4 T cells did not express IL-15. CD4 T cells lacked Il15 gene reporter activity, did not contain IL-15 transcripts, and did not produce IL-15Rα, the proprietary IL-15 receptor required for IL-15 trans-presentation. Moreover, IL-15 failed to inhibit Th17 cell differentiation and failed to generate Foxp3+ Treg cells in vitro. IL-2, which utilizes the same IL-2Rß/γc receptor complex, however, successfully did so. Exogenous IL-15 only exerted bioactivity and controlled T cell differentiation when it was trans-presented by IL-15Rα. Consequently, IL-15Rα-bound IL-15, but not free IL-15, suppressed Th17 cell differentiation and induced Treg cell generation. Collectively, these results reveal the absence of an IL-15 autocrine loop in CD4 T cells and strongly suggest that IL-15 trans-presentation by non-CD4 T cells is the primary mechanism via which IL-15 controls CD4 effector T cell differentiation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
/
Diferenciação Celular
/
Interleucina-15
Limite:
Animals
Idioma:
En
Revista:
Cytokine
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos