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Dendritic Cell Immunization Route Determines Integrin Expression and Lymphoid and Nonlymphoid Tissue Distribution of CD8 T Cells¹

Department of Microbiology and Carter Immunology Center, University of Virginia, Charlottesville, VA 22908

Exogenous dendritic cells (bone marrow-derived dendritic cell (BMDC)) display restricted trafficking in vivo after injection into mice, but the route(s) by which they generate gut-homing effector cells is unclear. Mesenteric lymph nodes (LN) and spleen were differentially targeted by i.p. and i.v. administration of BMDC, respectively, whereas mediastinal LN were targeted by both routes. BMDC injected by either route activated CD8⁺ T cells to up-regulate both ₄₁ and ₄₇ integrins. However, the lymphoid compartment in which activation occurred determined their expression kinetics, magnitude, and population distribution. Only T cells activated in mesenteric LN after i.p. immunization expressed high levels of ₄₇, which also correlated with localization to small intestine. These ₄₇^high cells also redistributed to mediastinal LN in a manner sensitive to treatment with ₄₇ blocking Abs, but not to mucosal addressin cell adhesion molecule-1 blocking Abs. Our results demonstrate the importance of lymphoid compartment, as dictated by immunization route, in determining integrin expression on activated T cells and their distribution in lymphoid and nonlymphoid tissues.

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 U.S. Public Health Service Grants CA78400, AI20963, and AI059996 (to V.H.E.). S.L.S.-O. was supported by Training Grant GM07627.

² Current address: College of Medicine, Pennsylvania State University, University Park, PA 16802.

³ Address correspondence and reprint requests to Dr. Victor H. Engelhard, Carter Immunology Center, University of Virginia, Box 801386, Charlottesville, VA 22908-1386. E-mail address: vhe{at}virginia.edu

⁴ Abbreviations used in this paper: DC, dendritic cell; BMDC, bone marrow-derived DC; HEV, high endothelial venule; int, intermediate; LN, lymph node; MAdCAM-1, mucosal addressin cell adhesion molecule-1; MFI, mean fluorescence intensity.

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