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The Journal of Immunology, 2007, 178: 4506-4516.
Copyright © 2007 by The American Association of Immunologists, Inc.

Collagen Distribution and Expression of Collagen-Binding {alpha}1beta1 (VLA-1) and {alpha}2beta1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection1

Martin Richter2,*, Steven J. Ray2,*, Timothy J. Chapman2,*, Sarah J. Austin*, Jonathan Rebhahn*, Timothy R. Mosmann*, Humphrey Gardner{dagger}, Victor Kotelianski{ddagger}, Antonin R. deFougerolles{ddagger} and David J. Topham3,*

* Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642; {dagger} Novartis Institutes for Biomedical Research, Cambridge, MA 02139; and {ddagger} Alnylam Pharmaceuticals, Cambridge, MA 02139

Most viral infections occur in extralymphoid tissues, yet the mechanisms that regulate lymphocytes in these environments are poorly understood. One feature common to many extralymphoid environments is an abundance of extracellular matrix. We have studied the expression of two members of the beta1 integrin family of collagen-binding receptors, {alpha}1beta1 and {alpha}2beta1 (CD49a, VLA-1 and CD49b, VLA-2, respectively), on CD4 and CD8 T cells during the response to influenza infection in the lung. Flow cytometry showed that whereas T cells infiltrating the lung and airways can express both CD49a and CD49b, CD49a expression was most strongly associated with the CD8+ subset. Conversely, though fewer CD4+ T cells expressed CD49a, most CD4+ cells in the lung tissue or airways expressed CD49b. This reciprocal pattern suggested that CD4 and CD8 T cells might localize differently within the lung tissue and this was supported by immunofluorescent analysis. CD8+ cells tended to localize in close proximity to the collagen IV-rich basement membranes of either the airways or blood vessels, whereas CD4+ cells tended to localize in the collagen I-rich interstitial spaces, with few in the airways. These observations suggest that CD4 T cell interaction with the tissue microenvironment is distinct from CD8 T cells and support the concept that CD4+ T cells in peripheral tissues are regulated differently than the CD8 subset.

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 in part by grants from the American Lung Association (RG-075N) and the National Institutes of Health (AG021970 and ESO1247). This work was also supported by National Institutes of Health Training Grants HL66988 (to S.J.R.), AI07169 (to T.J.C.), and HL6688 (to S.J.A.).

2 M.R., S.J.R., and T.J.C. contributed equally to this study.

3 Address correspondence and reprint requests to Dr. David J. Topham, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, 601 Elmwood Avenue, Box 609, Rochester, NY 14642. E-mail address: david_topham{at}urmc.rochester.edu

4 Abbreviations used in this paper: ECM, extracellular matrix; s.e., structuring element; MLN, mediastinal lymph node; PA, polymerase; NP, nucleoprotein.




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