Differential Microenvironment Localization of Effector and Memory CD8 T Cells

Abstract

CD8 T cells are critical for the clearance of intracellular pathogens. Upon infection, naive CD8 T cells differentiate into effector cells that target and eliminate infected cells. Following clearance of the pathogen, most effector cells die, although a small fraction survives to establish a memory population. Subsequent exposure to the same pathogen induces a rapid response of memory T cells and efficient elimination of the pathogen. Although much is known about the CD8 T cell response, the precise microenvironment location of effector and memory CD8 T cells in secondary lymphoid organs is not well characterized. In this study, we present an in situ analysis of the localization of effector and memory CD8 T cells during the murine immune response to lymphocytic choriomenginits virus. We identified the location of these cells using a transgenic mouse model system in which CD8 T cells are irreversibly tagged with yellow fluorescent protein (YFP) after activation. After infection, YFP+ CD8 T cells were initially observed within T cell zones. Later, these cells were found in the red pulp and a disruption of all CD8 T cell zones was observed. After resolution of the immune response, YFP+ memory CD8 T cells were observed primarily in T cells zones. Thus, in the spleens of mice, effector CD8 T cells localize to the red pulp and memory CD8 T cells localize to the T cell zones. Upon rechallenge, memory CD8 T cells rapidly proliferate and the secondary effector CD8 T cells are found in the red pulp.