CD27 co-stimulation controls tissue-specific memory CD8 T cell formation. (MUC3P.949)

Abstract

Abstract Memory CD8 T cells comprise niches of circulating cells and non-circulating tissue residents. The localization of memory cells defines phenotypic and functionally distinct populations. However, the mechanisms that direct tissue-specific T cell responses remain unclear. The co-stimulatory molecule CD27 is expressed on naïve cells and memory cells in secondary lymphoid and peripheral tissues. In response to virus infection, CD27 signals enhance the magnitude of effector CD8 T cells and their capacity to respond to subsequent pathogen challenge. Moreover, CD27 may actively maintain memory CD8 T cells in secondary lymphoid tissues. We previously reported that memory cells downregulate CD27 upon entry into peripheral tissues and acquire increased lytic potential. Thus our aim was to characterize the importance of CD27 signals during the formation of tissue-resident CD8 T cells. We determined that CD27 is critical for the generation of memory cells in secondary lymphoid tissues, however it is dispensable for tissue-resident memory cells. The defect was partially dependent on mTOR because administration of rapamycin during effector differentiation rescued memory formation in absence of CD27, despite no detectable effect on the magnitude of the effector response. Analysis of CD27low cells revealed functions distict from CD27hi memory cells. Downregulation of CD27 upon entry into the periphery may be an important event that enables CD8 T cells to take up tissue residence.