Intrinsic role of FoxO3a in the contraction of CD8+ T cell response (110.14)

Abstract

Abstract CD8+ T cells undergo rapid expansion during infection with intracellular pathogens, which is followed by swift and massive culling of primed CD8+ T cells. The mechanisms that govern the massive contraction of primed CD8+ T cells are not clear. We show that the transcription factor Foxo3a plays a key role in the contraction, not expansion, of CD8+ T cell response against Listeria monocytogenes (LM). FoxO3a-mutant OVA-specific CD8+ T cells isolated during peak of response displayed reduced expression of pro-apoptotic molecules BIM and PUMA, and underwent reduced apoptosis during contraction phase in comparison to WT cells. A higher number of memory precursor effector cells (MPECs) were detectable in FoxO3a-mutant mice compared to WT mice during contraction phase. Furthermore, FoxO3a-mutant OVA-specific CD8+ T cells upon transfer into normal mice underwent highly reduced contraction. These results show for the first time that FoxO3a acts in a cell intrinsic manner to promote the culling of primed CD8+T cells during the contraction phase.