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

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Abstract
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-γ+) and IFN-γ− CD4+ T cells recovered from lung parenchyma retained functional CCR7, whereas virus-specific IFN-γ-producing T cells were CCR7−. In contrast, a majority of virus-specific IFN-γ+ 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.