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

ABSTRACT: 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. T-bet was found to directly bind to and control the transcriptio

SUBMITTER: Villegas-Mendez A 

PROVIDER: S-EPMC7477746 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature