The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells.
Ray, John P. 1,5; Staron, Matthew M. 1,5; Shyer, Justin A. 1,5; Ho, Ping-Chih 1; Marshall, Heather D. 1; Gray, Simon M. 1; Laidlaw, Brian J. 1; Araki, Koichi 4; Ahmed, Rafi 4; Kaech, Susan M. 1,2,6,*; Craft, Joe 1,3,6,**
[Article] Immunity. 43(4):690-702, October 2015.

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SUMMARY: 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.

* Tfh cells are less proliferative and metabolically active than Th1 cells

* NFAT signaling is conserved in Tfh cells

* Tfh cells have minimal mTOR activity and are intact in the absence of mTORc1

* IL-2 suppresses Tfh cell differentiation through Akt activation

(C) 2015Elsevier, Inc.