The transcription factor AFF3 is necessary to maintain metabolic quiescence in naïve CD8 T cells and prevent premature immune aging

Naïve CD8 T cells must be maintained in a quiescent metabolic state in order to respond robustly to infection while avoiding inappropriate activation and causing immunopathology. With age this quiescent state is lost and the CD8 T cell response to infection decreases. The factors regulating metabolic quiescence of CD8 T cells and how this regulation is lost during aging are not completely understood. Herein, we identify the transcription factor AFF3 as a novel regulator of metabolic quiescence in naïve CD8 T cells. While naïve AFF3 deficient CD8 T cells are more metabolically active prior to infection, they have reduced accumulation in response to viral infection and this is correlated with a poor capacity to engage glycolysis. During aging in both murine and human CD8 T cells, AFF3 expression is reducing, correlating with to a loss of quiescent metabolism without the cells entering an activated state. Our data highlights the role of the metabolism in CD8 T cell quiescence and identifies a novel transcription factor that may be a target to reinvigorate CD8 T cell responses during aging.