Expression of programmed death–1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulator ligand on human respiratory tract epithelial cells and regulation by …

LA Stanciu, CM Bellettato, V Laza-Stanca… - The Journal of …, 2006 - academic.oup.com
LA Stanciu, CM Bellettato, V Laza-Stanca, AJ Coyle, A Papi, SL Johnston
The Journal of infectious diseases, 2006academic.oup.com
Background Respiratory syncytial virus (RSV) is associated with wheezing illness, and
infections can occur repeatedly throughout life. We hypothesized that RSV infection of
respiratory tract epithelial cells up-regulates B7 molecules that regulate memory immune
responses and that type 1 and 2 cytokines differentially modulate this induction Methods We
used flow-cytometric analysis to investigate programmed death–1 ligand (PD-L) 1, PD-L2,
B7-H3, and inducible costimulatory ligand (ICOS-L) expression on tracheal (NCI-H292) …
Abstract
BackgroundRespiratory syncytial virus (RSV) is associated with wheezing illness, and infections can occur repeatedly throughout life. We hypothesized that RSV infection of respiratory tract epithelial cells up-regulates B7 molecules that regulate memory immune responses and that type 1 and 2 cytokines differentially modulate this induction
MethodsWe used flow-cytometric analysis to investigate programmed death–1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulatory ligand (ICOS-L) expression on tracheal (NCI-H292), bronchial (BEAS-2B), and alveolar (A549) epithelial cells; regulation of this expression by RSV, interferon (IFN)–γ, and interleukin (IL)–4; and the effects of IFN-γ and IL-4 on RSV-induced expression of these molecules
ResultsB7-H3 was strongly expressed, PD-L1 and ICOS-L were moderately expressed, and PD-L2 was weakly expressed on unstimulated tracheal, bronchial, and alveolar epithelial cells. RSV infection up-regulated PD-L1, PD-L2, and B7-H3 expression on all cells and ICOS-L expression on bronchial and alveolar epithelial cells. IL-4 treatment alone had no effect, whereas IFN-γ treatment alone increased PD-L1 and PD-L2 expression on all cells and decreased B7-H3 expression on bronchial and alveolar epithelial cells. On RSV-infected alevolar epithelial cells, IFN-γ treatment increased PD-L1 and PD-L2 expression and decreased B7-H3 and ICOS-L expression, and IL-4 treatment increased PD-L2 and B7-H3 expression and decreased ICOS-L expression
ConclusionsRespiratory tract epithelial cells express a wide range of B7 molecules. RSV infection increases their expression, and this expression is differentially regulated by IFN-γ and IL-4. These processes may be involved in decreasing T cell antiviral immune responses to RSV and in RSV-associated wheezing
Oxford University Press