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Differentiation of Central Memory CD8 T Cells Is Independent of CD62L-Mediated Trafficking to Lymph Nodes¹

Thomas C. Wirth^*, Vladimir P. Badovinac, Lichao Zhao, Morris O. Dailey and John T. Harty^1,*,

^* Department of Microbiology, University of Iowa, Iowa City, IA 52242; Department of Pathology, University of Iowa, Iowa City, IA 52242; Department of Pathology, University of Oklahoma, Oklahoma City, OK 73104; and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242

CD62L (L-selectin) is a key regulator of T cell trafficking, and its surface expression on activated T cells is modulated to control T cell access to lymph nodes after acute infections. In memory T cells, CD62L is the most frequently used marker to define central memory T cells, a population that provides enhanced protection against most, but not all, pathogens. Early access of CD62L^pos effector T cells to lymph nodes has been proposed to result in preferential central memory T cell differentiation, but direct proof for the involvement of lymph node homing in memory T cell differentiation is lacking. In this study, we show that central memory lineage commitment in CD8 T cells is unaltered by enhanced entry into lymph nodes as a result of constitutive CD62L expression, and that equal numbers of effector and central memory CD8 T cells develop in the absence of CD62L-mediated lymph node trafficking. Our results suggest that CD62L is not a deterministic marker of central memory T cell differentiation, thus providing new insight into the process of memory CD8 T cell generation.

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 Address correspondence and reprint requests to Dr. John T. Harty, Department of Microbiology, University of Iowa, 3-530 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242. E-mail address: john-harty{at}uiowa.edu

² Abbreviations used in this paper: HEV, high endothelial venule; int, intermediate; LM-OVA, L. monocytogenes expressing OVA; LTA^–/–, lymphotoxin deficient; neg, negative; pos, positive; vir LM-OVA, virulent L. monocytogenes expressing OVA; VV-OVA, vaccinia virus expressing the SIINFEKL peptide; wt, wild type.