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 following 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 bronchial epithelial cells from normal human tissue responded to RSV infection with an increased expression of class I MHC as determined by flow cytometry and immunoprecipitation of class I MHC from metabolically radiolabeled cells. The increase in class I MHC expression was dependent on infectious, replicating virus. UV-irradiated culture supernatants from RSV-infected A549 cells, when added to fresh A549 cell cultures, induced an increase in class I MHC expression by those cells. The class 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 blocked the increase in class I MHC expression by cells treated with the above-mentioned supernatants. These results demonstrate that RSV infection elicits IFN-beta production by respiratory epithelial cells, which in turn leads to an increase in their synthesis of class I MHC, which would facilitate their recognition and lysis by RSV-specific CD8+ T cells.
Garofalo
R
R
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555, USA.
Mei
F
F
Espejo
R
R
Ye
G
G
Haeberle
H
H
Baron
S
S
Ogra
P L
PL
Reyes
V E
VE
D000276:Adjuvants, Immunologic / Q000502:physiology; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D004848:Epithelium; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D005805:Genes, MHC Class I / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000502:physiology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D016899:Interferon-beta