title: Airway epithelial cell damage mediated by antigen-specific T cells: implications in lung allograft rejection.
abstract: The aim of this study is to assess the mechanisms associated with airway epithelial cell (AEC) injury, which may have implications in lung allograft rejection. Three AEC lines, KDI-650, Beas-2B and A549 were analyzed. Effect of cytokines on the expression of Fas, HLA class I, and HLA class II were assessed by flow cytometry. AEC-specific T cells were generated in vitro and assessed for lysis by (51)Cr release assay. HLA class I and Fas were expressed on all AEC lines. Beas-2B and A549 expressed low levels of class II compared with KDI-650, which lack this expression. Expression of HLA class II was augmented on KDI-650 and Beas-2B by IFN-gamma treatment. AEC-specific T cells generated in vitro were predominantly CD8(+) and lysed relevant AEC targets. Anti-HLA class I monoclonal antibodies inhibited the lysis of AEC by specific T cells while anti-Fas and anti-HLA class II monoclonal antibodies did not have any effect on the T cell induced lysis of AECs. AECs cultured with supernatant derived from T-cell cultures induced the expression of Fas, HLA class I, as well as HLA class II. These results suggest AEC damage is mediated by AEC-specific T cells primarily by the conventional HLA class I/peptide complex and TCR interaction. Further, the factors released by these T cells also induce the expression of Fas, as well as HLA class I and class II, which may have implications on the outcome of the immune response against AECs.
authors.affiliation: Department of Surgery Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Jaramillo
authors.forename: B F
authors.initials: BF
authors.lastname: Duffy
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D019014:fas Receptor