HUMAN EOSINOPHILS PRODUCE BIOLOGICALLY-ACTIVE IL-12 - IMPLICATIONS FOR CONTROL OF T-CELL RESPONSES

The present study assessed the capacity of eosinophils (EOS) to synthe size the cytokine IL-12. Blood-derived, highly purified human EOS from six atopic patients and two nonatopic individuals were treated in cul ture with IL-4, IL-5, granulocyte-macrophage CSF, IFN-gamma, TNF-alpha , IL-1 alpha, RANTES, and complement 5a, respectively. The expression of both IL-12 protein and mRNAs for the p35 and p40 IL-12 subunits was strongly induced in all donors by the Th2-like cytokines IL-4 and gra nulocyte-macrophage CSF and was also moderately induced by TNF-alpha a nd IL-1 alpha. IL-5 treatment resulted in IL-12 synthesis in four atop ic donors and one nonatopic donor, whereas IFN-gamma induced IL-12 syn thesis in only two atopic donors. In contrast, RANTES exclusively indu ced mRNA for the p40 subunit without detectable protein release, and c omplement 5a had no effect on IL-12 mRNA or protein expression. EOS-de rived IL-12 was biologically active, because supernatants derived from IL-4-treated EOS superinduced the Con A-induced expression of IFN-gam ma by a human Th1-like T cell line. This activity was neutralized by a nti-IL-12 Abs. In conclusion, EOS secrete biologically active IL-12 af ter treatment with selected cytokines, which mainly represent the Th2- like type. Consequently, EOS may promote a switch from Th2-like to Th1 -like immune responses in atopic and parasitic diseases.