T cells from human allergen-induced late asthmatic responses express IL-12receptor beta 2 subunit mRNA and respond to IL-12 in vitro

IL-12 suppresses proallergic Th2-type cytokine production and induces Th1-t ype cytokine production by peripheral blood T cells from subjects with alle rgic disease. The objective of the present study was to examine the relevan ce of these findings to target organ. T cell responses in human asthma, Bro nchoalveolar lavage (BAL) and PBMC were collected from atopic asthmatics 24 h after fiberoptic allergen challenge of a segmental bronchus, BAL T cells and PBMC were cultured with allergen in the presence of recombinant IL-12 or IFN-gamma, and cytokines were measured in culture supernatants after 6 d ays. IL-5 production by BAL T cells and PBMC was inhibited by IL-12 and, to a lesser extent, by IFN-gamma. IL-12 also induced IFN-gamma production by BAL T cells and PBMC, The effects of IL-12 nor IFN-gamma on IL-5 production could not be reversed by neutralizing anti-IFN-gamma or anti-IL-12 mAbs, r espectively. Thus, the effect of neither IL-12 nor IFN-gamma appeared to be mediated through induction of the other cytokine, In situ hybridization re vealed that approximately one-third of BAL T cells expressed mRNA transcrip ts encoding the IL-12R beta2 subunit following allergen challenge. Thus, hu man T cells obtained from BAL during asthmatic late responses,like T cells in the peripheral circulation, remain susceptible to immunomodulation by IL -12, These findings raise the possibility that IL-12 may hold therapeutic p otential in allergic diseases such as asthma.