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Differential Microenvironment Localization of Effector and Memory CD8 T Cells¹

Joseph G. Dauner^*, Ifor R. Williams and Joshy Jacob^2,*

^* Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Center; and Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Emory University, Atlanta, GA 30322

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funds from the National Institutes of Health and the American Cancer Society.

² Address correspondence and reprint requests to Dr. Joshy Jacob, 954 Gatewood Road Northeast, Emory University, Atlanta, GA 30329. E-mail address: jjacob3{at}emory.edu

³ Abbreviations used in this paper: LCMV, lymphocytic choriomenginits virus; YFP, yellow fluorescent protein; GBC, granzyme B cre; β-gal, β-galactosidase; DC, dendritic cell.