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mTORc1

Exhausted CD4(+) T Cells during Malaria Exhibit Reduced mTORc1 Activity Correlated with Loss of T-bet Expression

September 15, 2020 - 10:16 -- Open Access
Author(s): 
Villegas-Mendez A, Khandelwal G, McGowan LM, Dookie RS, Haley MJ, George C, Sims D, Lord GM, Sinclair LV, Jenner RG, Couper KN
Reference: 
J Immunol. 2020 Sep 15;205(6):1608-1619

CD4+ T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with impaired parasite control and infection chronicity. However, the mechanisms of CD4+ T cell exhaustion are still poorly understood. In this study, we show that Ag-experienced (Ag-exp) CD4+ T cell exhaustion during Plasmodium yoelii nonlethal infection occurs alongside the reduction in mammalian target of rapamycin (mTOR) activity and restriction in CD4+ T cell glycolytic capacity. We demonstrate that the loss of glycolytic metabolism and mTOR activity within the exhausted Ag-expCD4+ T cell population during infection coincides with reduction in T-bet expression.

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