In vitro and in vivo induction of B7-H1 and B7-DC expression by human rhinovirus infection of airway epithelial cells (46.5)

Abstract

Abstract We have found that human airway epithelial cells express costimulatory molecules B7-H1, B7-H2, B7-H3 and B7-DC mRNA and cell-surface protein. IFN? and TNF? selectively induce B7-H1 and B7-DC and glucocorticoid fluticasone (FP) inhibits this induction. We now report that human rhinovirus infection (HRV-16), a key trigger of exacerbations of chronic rhinosinusitis and asthma, results in selective induction of B7-H1 and B7-DC expression in airway epithelial cells both in vitro and in vivo. In vitro exposure of human primary bronchial epithelial cells (PBEC) to HRV-16 (TCID50 5 X 103.1) resulted in induction of cell surface expression of B7-H1 as measured by flow cytometry (from 42±9 to 56±8 MFI, p<0.05) and B7-DC (from 5±1 to 9±2 MFI, p<0.01) (n=6). Pretreatment with FP (10-7 M) inhibited the induction of B7-H1 by 64% (p<0.05) and B7-DC by 95% (p<0.01). Additionally, in vitro exposure of PBEC to TLR3 agonist dsRNA (25 ug/ml), a surrogate for HRV16 infection, mirrored the effect of HRV-16 infection. Nasal scrapings taken at the time of peak symptom scores 4 days after infection of 6 human subjects with HRV-16 showed selective increases in levels of mRNA for B7-H1 (8.5±2.5 fold, p<0.03) and B7-DC (3.2±1.1 fold, p<0.07). These data show that exposure to TLR3 agonist dsRNA or HRV-16 infection induces B7-H1 and B7-DC on epithelial cells and this may influence the development of adaptive immune responses in the airways.