RESPIRATORY SYNCYTIAL VIRUS-INFECTION OF HUMAN RESPIRATORY EPITHELIAL-CELLS UP-REGULATES CLASS-I MHC EXPRESSION THROUGH THE INDUCTION OF IFN-BETA AND IL-1-ALPHA

CD8(+) T cells mediate some of the damage to the lung epithelium follo wing respiratory syncytial virus (RSV) infection. Since CD8(+) T cells recognize antigen-laden class I MHC molecules on the target cells, we examined in this study the expression of class I MHC by RSV-infected respiratory epithelial cells. Respiratory epithelial cell lines and br onchial epithelial cells from normal human tissue responded to RSV inf ection with an increased expression of class I MHC as determined by fl ow cytometry and immunoprecipitation of class I MHC from metabolically radiolabeled cells. The increase in class I MHC expression was depend ent on infectious, replicating virus. UV-irradiated culture supernatan ts from RSV-infected A549 cells, when added to fresh A549 cell culture s, induced an increase in class I MHC expression by those cells. The c lass I MHC increasing activity within supernatants from A549 cells was due, in large part, to IFN-beta, and to a lesser extent to IL-1 alpha . The addition of neutralizing Abs to both cytokines completely blocke d the increase in class I MHC expression by cells treated with the abo ve-mentioned supernatants. These results demonstrate that RSV infectio n elicits IFN-beta production by respiratory epithelial cells, which i n turn leads to an increase in their synthesis of class I MHC, which w ould facilitate their recognition and lysis by RSV-specific CD8(+) T c ells.