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CD8 T Cell Recall Responses Are Regulated by the Tissue Tropism of the Memory Cell and Pathogen¹

Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030

Whether memory CD8 T cells can be reactivated in nonlymphoid tissues is unclear. Using mice lacking the spleen, lymph nodes, or both, we show that the secondary T cell response, but not homeostatic maintenance of memory cells, required lymphoid tissue. Whereas primary and secondary CD8 T cell responses to vesicular stomatitis virus infection were lymph node dependent, responses to Listeria monocytogenes infection were driven primarily in the spleen. Memory cell subset reactivation was also regulated by location of the responding population and the pathogen. Thus, CD62L^low effector memory T cells (T_EM) cells responded nearly as well as CD62L^high central memory T cells (T_CM) and T_CM cells after L. monocytogenes infection, and both subsets generated equivalent populations of secondary memory cells. In contrast, T_CM cells, but not T_EM cells, mounted a robust response to vesicular stomatitis virus infection. T_CM and T_EM cells also required lymphoid tissue to mount recall responses, and the bone marrow did not contribute significantly to the response of either subset. Our findings indicated that characteristics of the infectious agent and the migratory preferences of memory cells dictated the secondary lymphoid tissue requirement for the recall response to infection.

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 National Institutes of Health Grants AI41576, DK45260, and PO1 AI56172 (to L.L.) and by National Institutes of Health Postdoctoral Fellowship AI53970 (to K.D.K.).

² These authors contributed equally to this work.

³ Current address: Department of Cellular Biology, University of Georgia, Athens, GA 30602.

⁴ Address correspondence and reprint requests to Dr. Leo Lefrançois, Department of Immunology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1319. E-mail address: llefranc{at}neuron.uchc.edu

⁵ Abbreviations used in this paper: T_CM, central memory T cells; T_EM, effector memory T cells; DC, dendritic cell; LN, lymph node; PP, Peyer’s patches; LCMV, lymphocytic choriomeningitis virus; LM-OVA, recombinant Listeria monocytogenes expressing OVA; LT, lymphotoxin ; VSV, vesicular stomatitis virus; PLN, peripheral lymph node; LP, lamina propria.

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