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

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.