T Cells from Human Allergen-Induced Late Asthmatic Responses Express IL-12 Receptor β2 Subunit mRNA and Respond to IL-12 In Vitro

• Published in: The Journal of immunology (1950) 2000-09, Vol.165 (5), p.2877-2885
• Main Authors: Varga, Eva Maria, Wachholz, Petra, Nouri-Aria, Kayhan T., Verhoef, Adrienne, Corrigan, Christopher J., Till, Stephen J., Durham, Stephen R.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.5.2877

IL-12 suppresses proallergic Th2-type cytokine production and induces Th1-type cytokine production by peripheral blood T cells from subjects with allergic disease. The objective of the present study was to examine the relevance of these findings to target organ T cell responses in human asthma. Bronchoalveolar 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-γ, and cytokines were measured in culture supernatants after 6 days. IL-5 production by BAL T cells and PBMC was inhibited by IL-12 and, to a lesser extent, by IFN-γ. IL-12 also induced IFN-γ production by BAL T cells and PBMC. The effects of IL-12 nor IFN-γ on IL-5 production could not be reversed by neutralizing anti-IFN-γ or anti-IL-12 mAbs, respectively. Thus, the effect of neither IL-12 nor IFN-γ appeared to be mediated through induction of the other cytokine. In situ hybridization revealed that approximately one-third of BAL T cells expressed mRNA transcripts encoding the IL-12R β2 subunit following allergen challenge. Thus, human 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 potential in allergic diseases such as asthma.