Different role of CD30 in the development of acute and chronic airway inflammation in a murine asthma model.
CD30 is a costimulatory molecule of the TNF receptor superfamily, expressed on activated T and B cells. Previously, we have shown in a murine asthma model the crucial role of CD30 signaling for the development of this Th2-cell-mediated disease. In the present study, we investigated the role of CD30 in the maintenance of the immune response. In contrast to the acute model, in the chronic model CD30(-/-) mice developed a severe asthma-like phenotype with eosinophilic inflammation and high serum IgE levels. Collagen content, ECM protein deposition and proliferation of smooth muscle cells as signs for airway remodeling were equally increased in both CD30(-/-) and WT mice. Reduced expression of the costimulatory molecule OX40 on CD3(+) T cells in the acute and up-regulation in the chronic model indirectly supported a compensatory role of OX40 for CD30 signaling. In accordance, application of agonistic OX40 antibody restored the asthma phenotype in CD30(-/-) mice in the acute model, whereas chronic airway inflammation was reduced in the presence of an inhibitory anti-OX40 ligand antibody. These data demonstrate that the crucial role of CD30 signaling in the development of acute asthma may be taken over by other costimulatory molecules like OX40 after long-term exposure to the antigen.
Polte
Tobias
T
Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, Germany.
Fuchs
Lena
L
Behrendt
Ann-Kathrin
AK
Hansen
Gesine
G
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000097:blood; D017730:Ki-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D053262:Receptors, OX40 / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin