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Sequential Activation of CD8⁺ T Cells in the Draining Lymph Nodes in Response to Pulmonary Virus Infection¹

Heesik Yoon^*, Kevin L. Legge^*,¶, Sun-sang J. Sung and Thomas J. Braciale^2,*,,

^* Carter Immunology Center and Department of Pathology, Department of Microbiology, and Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, VA 22908; and ^¶ Department of Microbiology, University of Iowa, Iowa City, IA 52242

We have used a TCR-transgenic CD8⁺ T cell adoptive transfer model to examine the tempo of T cell activation and proliferation in the draining lymph nodes (DLN) in response to respiratory virus infection. The T cell response in the DLN differed for mice infected with different type A influenza strains with the onset of T cell activation/proliferation to the A/JAPAN virus infection preceding the A/PR8 response by 12–24 h. This difference in T cell activation/proliferation correlated with the tempo of accelerated respiratory DC (RDC) migration from the infected lungs to the DLN in response to influenza virus infection, with the migrant RDC responding to the A/JAPAN infection exhibiting a more rapid accumulation in the lymph nodes (i.e., peak migration for A/JAPAN at 18 h, A/PR8 at 24–36 h). Furthermore, in vivo administration of blocking anti-CD62L Ab at various time points before/after infection revealed that the virus-specific CD8⁺ T cells entered the DLN and activated in a sequential "conveyor belt"-like fashion. These results indicate that the tempo of CD8⁺ T cell activation/proliferation after viral infection is dependent on the tempo of RDC migration to the DLN and that T cell activation occurs in an ordered sequential fashion.

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 AI-15608, HL-33391, and AI-37293 (to T.J.B.) and HL-70065 (to S.J.S.). K.L.L. was supported by the Cancer Research Institute.

² Address correspondence and reprint requests to Dr. Thomas J. Braciale, Carter Immunology Center, University of Virginia, P.O. Box 801386, Charlottesville, VA 22908. E-mail address: tjb2r{at}virginia.edu

³ Abbreviations used in this paper: SLO, secondary lymphoid organ; DC, dendritic cell; LN, lymph node; HEV, high endothelial venule; RDC, respiratory DC; DLN, draining LN; Tg, transgenic; RT, room temperature; LYVE-1, lymphatic endothelium hyaluronic acid receptor 1; i.n., intranasal(ly); HA, hemagglutinin; p.i., postinfection; NDLN, nondraining LN; CL-4, Clone-4.