The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells.
Immunity
; 43(4): 690-702, 2015 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-26410627
ABSTRACT
The differentiation of CD4(+) helper T cell subsets with diverse effector functions is accompanied by changes in metabolism required to meet their bioenergetic demands. We find that follicular B helper T (Tfh) cells exhibited less proliferation, glycolysis, and mitochondrial respiration, accompanied by reduced mTOR kinase activity compared to T helper 1 (Th1) cells in response to acute viral infection. IL-2-mediated activation of the Akt kinase and mTORc1 signaling was both necessary and sufficient to shift differentiation away from Tfh cells, instead promoting that of Th1 cells. These findings were not the result of generalized signaling attenuation in Tfh cells, because they retained the ability to flux calcium and activate NFAT-transcription-factor-dependent cytokine production. These data identify the interleukin-2 (IL-2)-mTORc1 axis as a critical orchestrator of the reciprocal balance between Tfh and Th1 cell fates and their respective metabolic activities after acute viral infection.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Subgrupos de Linfocitos T
/
Interleucina-2
/
Linfocitos T Colaboradores-Inductores
/
Complejos Multiproteicos
/
Proteínas Proto-Oncogénicas c-akt
/
Serina-Treonina Quinasas TOR
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos