TY - JOUR
T1 - Airway epithelial cell damage mediated by antigen-specific T cells
T2 - Implications in lung allograft rejection
AU - Smith, Craig R.
AU - Jaramillo, Andrés
AU - Duffy, Brian F.
AU - Mohanakumar, T.
PY - 2000
Y1 - 2000
N2 - 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-Fa 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. (C) American Society for Histocompatibility and Immunogenetics, 2000.
AB - 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-Fa 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. (C) American Society for Histocompatibility and Immunogenetics, 2000.
KW - Airway epithelial cells
KW - Cytokines
KW - Lung allograft
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=0033696644&partnerID=8YFLogxK
U2 - 10.1016/S0198-8859(00)00175-0
DO - 10.1016/S0198-8859(00)00175-0
M3 - Article
C2 - 11082511
AN - SCOPUS:0033696644
SN - 0198-8859
VL - 61
SP - 985
EP - 992
JO - Human Immunology
JF - Human Immunology
IS - 10
ER -