CD40L, but not CD40, is required for allergen-induced bronchial hyperresponsiveness in mice

Asthma is characterized by immunoglobulin (Ig) E production, infiltration o f the respiratory mucosa by eosinophils (EOSs) and mononuclear cells, and b ronchial hyperresponsiveness (BHR). Interaction of CD40 on B cells and anti gen presenting cells, with its ligand (CD40L) expressed transiently on acti vated T cells, is known to augment both T cell-driven inflammation and humo ral immune responses, especially IgE production, Considering both the promi nent role of inflammation in asthma and the association of the disease with IgE, we hypothesized that CD40-CD40L interactions would be important in pa thogenesis. To test this hypothesis, we subjected wild-type (WT) mice and a nimals lacking either CD40 or CD I OL to repeated inhalation of Aspergillus fumigatus (Af) antigen. Af-treated WT mice displayed elevated IgE levels, bronchoalveolar lavage and pulmonary tissue eosinophilic inflammation, and BHR. IgE production was markedly suppressed in both the CD40 -/- and CD40L -/- strains. However, pulmonary inflammation did not appear to be inhibited by either of these mutations. Paradoxically, development of BHR was preven ted by the lack of CD40L but not by the absence of CD40. We conclude that C D40/CD40L interactions, although critical in the induction of IgE responses to inhaled allergen, are not required for the induction of EOS-predominant inflammation. CD40L, but not CD40, is necessary for the development of all ergen-induced BHR.