Differential requirement for CCR7 expression in primary and secondary CD8 T cell responses to infection (69.9)

Abstract

Abstract Since naïve and memory T cells localize in both red and white pulp of the spleen, we wished to test the relative contribution of priming in each location. To do so, we employed TCR transgenic CD8 T cells (OT-I) that either lacked CCR7 or constitutively expressed CCR7 (CD2-CCR7). After Listeria infection, CCR7-/- CD8 T cells did not enter the T cell zone (PALS) while CD2-CCR7 OT-I cells were confined nearly exclusively to the PALS. The response of CCR7-/-CD8 T cells was blunted compared to WT and CD2-CCR7 OT-I cells and was characterized by skewing toward KLRG1highCD127low short-lived effector cells (SLEC) and away from KLRG1lowCD127high memory precursor effector cells (MPEC). Transfer studies showed that CCR7-/- OT-I cells competed with endogenous ova-specific CD8 T cells, suggesting that some priming occurred in the red pulp in normal conditions. Interestingly, CCR7-/-, CD2-CCR7 and WT OT-I memory cells responded equally well to challenge infection indicating a low stringency for localization for memory CD8 T cell activation. These results suggested that antigen presentation in the red pulp promoted SLEC generation while white pulp priming promoted MPEC development, perhaps due to differences in the inflammatory milieu. Along with our demonstration that naïve and memory CD8 T cell activation exhibited distinct anatomical requirements, our findings implied that local environmental cues regulated the development of primary and secondary CD8 T cell responses to infection.