Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung

The lungs are frequently challenged by viruses, and resident CD8(+) T cells likely contribute to the surveillance of these pathogens. To obtain insight into local T cell immunity to respiratory viruses in humans, we determined the specificity, phenotype, and function of lung-residing CD8(+) T cells and peripheral blood CD8(+) T cells in a paired analysis. The lung contained markedly higher frequencies of influenza (FLU)-specific and respiratory syncytial virus (RSV)-specific CD8(+) T cells when compared with the circulation. This contrasted with an equal distribution of cytomegalovirus- and Epstein-Bar virus-specific CD8(+) T cells. Noticeably, a substantial fraction of the lung-residing FLU- and RSV-specific CD8(+) T cells had progressed to a relatively late differentiation phenotype, reflected by low expression of CD28 and CD27. Lung-derived FLU- specific CD8(+) T cells had low activation requirements, as expansion of these cells could be initiated by cognate peptide in the absence of helper cell-derived signals. Thus, the human lung contains high numbers of differentiated FLU- and RSV-specific memory CD8(+) T cells that can readily expand upon reexposure to virus. Resident lung T cells may provide immediate immunological protection against pulmonary virus infections.