Constitutive and Inducible Expression of B7 Family of Ligands by Human Airway Epithelial Cells
- 1 September 2005
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 33 (3), 280-289
- https://doi.org/10.1165/rcmb.2004-0129oc
Abstract
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 interferon (IFN)-gamma (100 ng/ml). The combination of IFN-gamma and tumor necrosis factor-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 with 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.Keywords
This publication has 58 references indexed in Scilit:
- Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infectionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- CD40-mediated Activation of NF-κB in Airway Epithelial CellsPublished by Elsevier BV ,2002
- Acute Sinusitis: A Histopathological and Immunohistochemical StudyThe Laryngoscope, 2000
- T lymphocytes that infiltrate nasal polyps have a specialized phenotype and produce a mixed TH1 /TH2 pattern of cytokinesJournal of Allergy and Clinical Immunology, 1998
- CD40 is functionally expressed on human keratinocytesEuropean Journal of Immunology, 1996
- CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.The Journal of Experimental Medicine, 1995
- CTLA-4 can function as a negative regulator of T cell activationImmunity, 1994
- CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clonesNature, 1992
- Human bronchial epithelial cells modulate CD3 and mitogen-induced DNA synthesis in T cells but function poorly as antigen-presenting cells compared to pulmonary macrophagesJournal of Allergy and Clinical Immunology, 1991
- Regulation of Interleukin-2 Gene Enhancer Activity by the T Cell Accessory Molecule CD28Science, 1991