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.
de Bree
Godelieve J
GJ
Department of Pulmonology, Academic Medical Center, University of Amsterdam, Netherlands. g.j.debree@amc.uva.nl
van Leeuwen
Ester M M
EM
Out
Theo A
TA
Jansen
Henk M
HM
Jonkers
René E
RE
van Lier
René A W
RA
D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte