title: CD8⁺ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung.
abstract: The human lung T cell compartment contains many CD8⁺ T cells specific for respiratory viruses, suggesting that the lung is protected from recurring respiratory infections by a resident T cell pool. The entry site for respiratory viruses is the epithelium, in which a subset of lung CD8⁺ T cells expressing CD103 (αE integrin) resides. Here, we determined the specificity and function of CD103⁺CD8⁺ T cells in protecting human lung against viral infection. Mononuclear cells were isolated from human blood and lung resection samples. Variable numbers of CD103⁺CD8⁺ T cells were retrieved from the lung tissue. Interestingly, expression of CD103 was seen only in lung CD8⁺ T cells specific for influenza but not in those specific for EBV or CMV. CD103⁺ and influenza-reactive cells preferentially expressed NKG2A, an inhibitor of CD8⁺ T cell cytotoxic function. In contrast to CD103⁻CD8⁺ T cells, most CD103⁺CD8⁺ cells did not contain perforin or granzyme B. However, they could quickly upregulate these cytotoxic mediators when exposed to a type I IFN milieu or via contact with their specific antigen. This mechanism may provide a rapid and efficient response to influenza infection, without inducing cytotoxic damage to the delicate epithelial barrier.
authors.affiliation: Department of Experimental Immunology, Academic Medical Centre, Amsterdam, Netherlands. b.piet@amc.nl
authors.forename: Berber
authors.initials: B
authors.lastname: Piet
authors.forename: Godelieve J
authors.initials: GJ
authors.lastname: de Bree
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Smids-Dierdorp
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.forename: Jan H
authors.initials: JH
authors.lastname: von der Thüsen
authors.forename: Jan M W
authors.initials: JM
authors.lastname: van Haarst
authors.forename: Jan P
authors.initials: JP
authors.lastname: Eerenberg
authors.forename: Anja
authors.initials: A
authors.lastname: ten Brinke
authors.forename: Wim
authors.initials: W
authors.lastname: van der Bij
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: René E
authors.initials: RE
authors.lastname: Jonkers
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001773:Blood Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004848:Epithelium / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis / Q000235:genetics; D006564:Herpesviridae / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology*; D039001:Integrin alpha Chains / Q000032:analysis; D039222:Integrin alpha1beta1 / Q000032:analysis; D008168:Lung / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000032:analysis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000235:genetics; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D039222:Integrin alpha1beta1; C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; C091367:alpha E integrins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes