CD27 costimulation is not critical for the development of asthma and respiratory tolerance in a murine model.
CD27 is a costimulatory molecule of the TNFR family strongly expressed on activated CD4(+) and CD8(+) T lymphocytes. Binding with its ligand CD70, present on lymphocytes and DCs, leads to enhanced T cell activation and proliferation. Several other costimulatory molecules of the TNFR family like CD30, CD134 (OX40) or CD137 (4-1BB) have been shown to be critically involved in the development of asthma and/or respiratory tolerance. However, the role of CD27/CD70 signalling in these disease models has not been studied intensively. The aim of this study was to directly investigate the role of CD27 for the development of asthma and respiratory tolerance by comparative analysis of wild type (WT) and CD27(-/-) mice in the corresponding murine models. Ovalbumin (OVA)-sensitized and challenged CD27(-/-) mice developed comparably increased airway hyperreactivity (AHR), eosinophilic airway inflammation, mucus hypersecretion and elevated OVA-specific serum IgE levels in response to OVA sensitization as WT mice. In addition, Th2 cytokine production in spleen cell culture supernatants and proliferation of splenocytes after in vitro OVA restimulation was equally enhanced when derived from WT and CD27(-/-) mice. Furthermore, the absence of CD27 had no decisive impact on tolerance induction, so that WT and CD27(-/-) mice were comparably protected from asthma development by mucosal antigen application before sensitization. Our results suggest that CD27 costimulation is dispensable for a Th2 cell mediated allergic asthma response and respiratory tolerance induction in murine models.
Behrendt
Ann-Kathrin
AK
Hannover Medical School, Department of Paediatric Pulmonology, Allergology and Neonatology, 30625 Hannover, Germany.
Hansen
Gesine
G
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007114:Immunization; D007073:Immunoglobulin E / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism; D011657:Pulmonary Eosinophilia; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007073:Immunoglobulin E; D010047:Ovalbumin