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Journal of Virology, July 2004, p. 7528-7535, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7528-7535.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CC Chemokine Receptor 7 Expression by Effector/Memory CD4⁺ T Cells Depends on Antigen Specificity and Tissue Localization during Influenza A Virus Infection

Experimentelle Rheumatologie, Medizinische Klinik, Charité, Humboldt Universität,¹ Deutsches Rheumaforschungszentrum, 10117 Berlin,² Robert Koch-Institut, NG2, 13353 Berlin,³ Universitätsklinikum Schleswig-Holstein, Campus Kiel, Nephrologisches Forschungslabor, 24105 Kiel, Germany⁴

Received 5 January 2004/ Accepted 15 March 2004

The lung is an important entry site for respiratory pathogens such as influenza A virus. In order to combat such invading infectious agents, effector/memory T cells home to the lung and other peripheral tissues as well as lymphoid organs. In this process, chemokines and their receptors fulfill important roles in the guidance of T cells into such organs and specialized microenvironments within tissues. In this study, we determined if CD4⁺ T cells residing in different lung compartments and draining lymph nodes of influenza A virus-infected and naïve mice express receptors allowing their recirculation into secondary lymphoid tissues. We found high levels of L-selectin and CC chemokine receptor 7 (CCR7) expression in lung-derived CD4⁺ T cells, similar to that detected on T cells in secondary lymphoid organs. Upon influenza A virus infection, the bulk of gamma interferon-positive (IFN-⁺) and IFN-^– CD4⁺ T cells recovered from lung parenchyma retained functional CCR7, whereas virus-specific IFN--producing T cells were CCR7^–. In contrast, a majority of virus-specific IFN-⁺ T cells in the lung draining lymph node were CCR7⁺. Independent of infection, CD4⁺ T cells obtained from the lung airways exhibited the lowest expression level of L-selectin and CCR7, indicating that T cells at this anatomical site represent the most differentiated effector cell type, lacking the ability to recirculate. Our results suggest that effector/memory T cells that enter inflammatory sites retain functional CCR7 expression, which is lost only upon response to viral antigen and after localization to the final effector site.

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