Direct evidence for a critical role of CD30 in the development of allergic asthma.

Abstract

BACKGROUND: CD30 is a costimulatory molecule belonging to the TNF receptor superfamily that is expressed on activated T and B cells. Several studies have demonstrated a positive correlation between expression of CD30 or increased levels of soluble CD30 and the development and severity of allergic diseases. However, thus far, the evidence for a role of CD30 in allergic diseases, such as asthma, is only indirect. OBJECTIVE: The aim of the study was to directly investigate the role of CD30 in a murine asthma model. METHODS: CD30-deficient (B6.129P2-Tnfrsf8(tm1Mak)/J) and wild-type (WT) mice were immunized to ovalbumin (OVA) to induce an asthma-like phenotype and compared in our murine asthma model. Moreover, CD30/CD30 ligand signaling was blocked in OVA-immunized WT animals by using mAbs against CD30 receptor and its ligand, CD153. RESULTS: The absence of CD30 in OVA-immunized CD30-deficient mice resulted in significantly reduced airway inflammation, serum IgE levels, and TH2 cytokine levels. The same effect was observed when CD30/CD153 signaling was blocked in OVA-immunized WT animals with mAbs against CD30 or CD30 ligand. CONCLUSION: Our results directly demonstrate that CD30/CD153 interaction plays an important role in the induction of TH2 cell-mediated allergic asthma. CLINICAL IMPLICATIONS: These findings provide evidence for a role of the costimulatory molecule CD30 in allergic asthma.