Induction of Th1 cell-mediated protective immunity to Schistosoma mansoni by co-administration of larval antigens and IL-12 as an adjuvant.

Abstract

In this study, rIL-12, which is a powerful inducer of Th1 lymphocyte development, was administered to mice as an adjuvant in conjunction with a soluble lung-stage Ag preparation (SLAP) derived from lung-stage larvae of Schistosoma mansoni to potentiate Th1-mediated immune responses and induce resistance to reinfection. Immunization of mice with one or two doses of SLAP + IL-12 elicited a dominant population of Ag-specific Th1 lymphocytes in the draining lymph nodes, as judged by the secretion of abundant IFN-gamma but undetectable levels of IL-4, upon antigenic restimulation in vitro. In contrast, SLAP alone induced a mixed population of Th1 and Th2 cells with secretion of IFN-gamma, IL-4, and IL-10. The development of a biased Th1 cell population in mice immunized with SLAP + IL-12 was reflected in enhanced levels of Ag-specific IgG2a but decreased levels of IgG1 and total IgE serum Abs. Ablation of NK1.1+ cells before the administration of a single dose of SLAP + IL-12 reduced Th cell proliferation and almost completely inhibited secretion of IFN-gamma by in vitro-cultured lymph node cells. This indicates that NK cells stimulated by IL-12 shortly after vaccination are critical to the subsequent development of Ag-specific Th1 cells. Finally, it is demonstrated that the delivery of two doses of SLAP + IL-12 to mice is sufficient to elicit moderate but highly significant levels of protective immunity against challenge infection.