IL-10 regulates early IL-12-mediated immune responses induced by the radiation-attenuated schistosome vaccine

Abstract

Radiation-attenuated (RA) schistosomes penetrate the host via the skin where they stimulate intense inflammatory reactions and the release of pro-inflammatory IL-12, important for Th1-type immune responses which are partially host protective. However, RA larvae also induce the secretion of regulatory IL-10. We now show that following vaccination of IL-12p40-/- mice, abundant IL-10 was produced by in vitro cultured skin biopsies between days 4 and 14, corresponding to the down-regulation of MHC II expression by cells in the dermis and cells that emigrate from the skin. In IL-10-/- mice, inflammation of the vaccination site was increased with larger numbers of IL-12p4O+, MHC II+ and CD86+ cells in the dermal exudate, and was associated with elevated levels of skin-derived IL-12p4O and IL-1β. These changes in IL-10-/- mice were also reflected by an increased number of cells in the skin-draining lymph nodes (sdLN) and greater levels of lymphocyte proliferation. Moreover, such mice had increased numbers of CD4+ sdLN cells that were CD25+, CD28+ or CD152+ and accessory cells that were CD40+ or MHC II+. Finally, the secretion of IFN-γ (and IL-12p4O) by in vitro cultured sdLN cells was substantially raised in IL-10-/- mice, but much reduced in IL-12p4-/- mice, resulting in the development of highly polarized Th1 and Th2 cytokine profiles in the two groups of mice respectively. We conclude that IL-10 has an important role early in the regulation of IL-12-mediated priming of acquired immune responses, and effectively contains excessive dermal inflammation and prevents the development of highly polarized Th1-type responses.