The role of sphingosine-1-phosphate receptor-1 in antigen-specific CD8 T cell migration (173.14)

Abstract

Abstract Our previous studies have helped illuminate the landscape in which the endogenous CD8 T cell immune response occurs. However, the factors that regulate the anatomical program that antigen-specific CD8 T follow after infection are not well understood. Although, it is known that sphingosine-1-phosphate receptor 1 (S1P1) controls naïve T cell trafficking, our understanding of how S1P1 regulates the migration and differentiation of CD8 T cells after infection remains poor. Here we investigated the role of S1P1 in the migration and localization of antigen-specific CD8 T cells in the lymph node (LN) after viral infection. We utilized pharmacological modulation of S1P1 and cell-specific S1P1 knock out mouse models to reveal a central role of S1P1 in controlling effector CD8 T cell migration from the draining LN. In the absence of S1P1 receptor signaling, antigen-specific CD8 T cells failed to utilize the lymphatic sinuses to egress from the draining LN. Furthermore, we used a novel mouse model that contains a mutated native S1P1 protein that cannot be efficiently internalized. Using this mouse model we show that receptor internalization can regulate effector CD8 T cell response early after infection. Therefore, our studies demonstrate that S1P1 receptor signaling is the dominant factor that regulates endogenous effector CD8 T cell migration in secondary lymphoid organs.