Differential localization of effector and memory T cell subsets (83.16)

Abstract

Abstract During viral infections, it is not well defined where within tissues effector and memory CD8 T cells form and persist. Our recent findings show that two subsets of effector CD8 T cells that have distinct cell fates are formed during acute infection - the KLRG1hi IL-7Rlo short-lived effector cells (SLECs) and the KLRG1lo IL-7Rhi memory precursor effector cells (MPECs). Most of the SLECs undergo apoptosis after infection whereas most MPECs survive and become long-lived memory T cells. Here, we show that MPECs and SLECs are differentially localized within the spleen during LCMV infection. Using immunofluorescence microscopy, we demonstrate that the majority of MPECs were found in the T cell zone, while SLECs were exclusively localized in the red pulp during the course of an immune response to LCMV infection. At memory time points, only T cells with an MPEC phenotype were found in the T cell zone. MPECs homed to the T cell zone using pertussis toxin-sensitive chemokine receptors, and appeared to contact with gp38+ stromal cells, which produce chemokines CCL19 and CCL21 and the T cell survival cytokine IL-7. Employing a transwell migration assay, we found that MPECs showed higher chemotactic ability toward CCL19 than SLECs. Together, our data suggest that the preferential survival of the MPECs and the memory T cells may be tightly linked to their localization in the T cell zone and the interaction with IL-7-producing stromal cells.