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
51Cr 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-γ 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.