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Published ahead of print on June 16, 2005, doi:10.1165/rcmb.2004-0129OC

Am. J. Respir. Cell Mol. Biol., Volume 33, Number 3, September 2005, 280-289

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Submitted on April 22, 2004
Revised on June 15, 2005

Constitutive and Inducible Expression of B7 Family of Ligands by Human Airway Epithelial Cells

Jean Kim1*, Allen C Myers2, Lieping Chen3, Drew Pardoll4, Quynh-Ai Truong-Tran5, Andrew Lane1, John McDyer6, Lowella Fortuno2, and Robert P Schleimer5

1 Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Department of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 3 Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 Allergy-Immunology Division, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, 6 Department of Pulmonary Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: jeankim{at}jhmi.edu.

Activated T cells have been implicated in chronic rhinosinusitis (CRS) and asthma and physically interact with epithelial cells in the airways. We now report that human airway epithelial cells display significant constitutive cell-surface expression of costimulatory ligands, B7-H1, B7-H2, B7-H3, and B7-DC. Expression of B7-H1 and B7-DC was selectively induced by stimulation of either BEAS2B or primary nasal epithelial cells (PNEC) with IFN{gamma} (100 ng/ml). The combination of IFN{gamma} and TNF{alpha}, (100 ng/ml) selectively induced expression better than IFN{gamma} alone. Fluticasone treatment(10-7 M) reduced the baseline expression and inhibited the induction of B7-H1 and B7-DC in BEAS2B cells. In vitro exposure of PNEC to IFN{gamma} also resulted in selective induction of B7-H1 and B7-DC. Monoclonal antibody blockade of B7-H1 or B7-DC enhanced IFN{gamma} expression by purified T cells in co-culture experiments, suggesting that these two B7 homologs inhibit T cell responses at the mucosal surface. Immunohistochemical staining of human sinonasal surgical tissue confirmed the presence of B7-H1, B7-H2 and B7-H3 in the epithelial cell layer, especially in samples from patients diagnosed with Samter's Triad, a severe form of CRS. Real time PCR analysis of sinonasal tissue revealed elevated levels of B7-H1 and B7-DC in CRS compared to controls. These results demonstrate that epithelial cells express functional B7 costimulatory molecules and that expression of selected B7 family members is inducible in vitro and in vivo. Epithelial B7 homologs could play a role in regulation of lymphocytic activity at mucosal surfaces.




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