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The Journal of Immunology, 2008, 180: 2957-2966.
Copyright © 2008 by The American Association of Immunologists, Inc.

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Proliferative Expansion and Acquisition of Effector Activity by Memory CD4+ T Cells in the Lungs following Pulmonary Virus Infection1

Erika L. Wissinger*,{ddagger}, Whitney W. Stevens*,{ddagger}, Steven M. Varga*,§ and Thomas J. Braciale2,*,{dagger},{ddagger}

* The Carter Immunology Center, {dagger} Department of Pathology, and {ddagger} Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, VA 22908; and § Department of Microbiology, University of Iowa, Iowa City, IA 52242

The memory CD4+ T cell response to the respiratory syncytial virus (RSV) attachment (G) protein in the lungs of primed BALB/c mice undergoing challenge pulmonary RSV infection is dominated by effector T cells expressing a single Vβ-chain, Vβ14. We have used Vβ14 expression to examine the kinetics of the activation, accumulation, and acquisition of the effector activity of memory CD4+ T cells responding to pulmonary infection. This analysis revealed that proliferative expansion and effector CD4+ T cell differentiation preferentially occur in the respiratory tract following rapid activation within and egress from the lymph nodes draining the respiratory tract. These findings suggest that, in response to natural infection at a peripheral mucosal site such as the lungs, memory CD4+ T cell expansion and differentiation into activated effector T cells may occur predominantly in the peripheral site of infection rather than exclusively in the lymph nodes draining the site of 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 AI37293, AI15608, and HL33391 (to T.J.B.), grants from the Parker B. Francis Foundation and the Virginia Thoracic Society/American Lung Association (to S.M.V.), and U. S. Public Health Service Grant T32 AI07496 (to E.L.W.).

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: RSV, respiratory syncytial virus; DLN, draining lymph node; DTH, delayed-type hypersensitivity; PBLN, peribronchial lymph node; p.i., postinfection; S1PR, sphingosine-1-phosphate receptor; vvG, vaccinia virus expressing RSV G glycoprotein; vvβ-gal, vaccinia virus expressing β-galactosidase.







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