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

• Published in: Journal of virology Vol. 78; no. 14; pp. 7528 - 7535
• Main Authors: Debes, G F, Bonhagen, K, Wolff, T, Kretschmer, U, Krautwald, S, Kamradt, T, Hamann, A
• Format: Journal Article
• Language: English
• Published: 15-07-2004
• Subjects: Influenza A virus
• ISSN: 0022-538X
• DOI: 10.1128/JVI.78.14.7528-7535.2004

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 super(+) T cells residing in different lung compartments and draining lymph nodes of influenza A virus-infected and naive 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 super(+) 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- gamma super(+)) and IFN- gamma super(-) CD4 super(+) T cells recovered from lung parenchyma retained functional CCR7, whereas virus-specific IFN- gamma -producing T cells were CCR7 super(-). In contrast, a majority of virus-specific IFN- gamma super(+) T cells in the lung draining lymph node were CCR7 super(+). Independent of infection, CD4 super(+) 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.