Antigens derived from lung-stage larvae of Schistosoma mansoni are efficient stimulators of proliferation and gamma interferon secretion by lymphocytes from mice vaccinated with attenuated larvae

Abstract

Protective immunity in C57BL/6 mice exposed to optimally irradiated larvae of Schistosoma mansoni operates against challenge parasites in the lungs and is dependent upon T-helper 1 (Th1) lymphocytes which secrete abundant gamma interferon (IFN-γ). As an initial step in the identification of the molecules which mediate this immunity, antigenic materials released by larvae at various times during in vitro culture were compared for the ability to induce proliferation of lymph node cells recovered from mice 4 to 6 days after exposure to attenuated parasites. Cells from mice vaccinated with cercariae proliferated most strongly to larval antigens released soon after transformation. In contrast, cells from mice immunized with lung-stage schistosomula responded poorly to these early secretions but proliferated vigorously to antigens released by older larvae. In further studies on the cytokine profile of the responding lymphocytes, it was observed that the balance between IFN-γ and interleukin-4 (IL-4) secretion depended on the source of antigen used for restimulation. Thus, material released between days 6 and 8 by in vitro-cultured larvae, and the soluble extracts of whole lung-stage larvae, induced abundant IFN-γ but little IL-4. This finding implies that an overwhelming proportion of the lymphocytes responsive to lung-stage antigens had the Th1 phenotype. In contrast, antigens from cercariae and skin-stage larvae induced the lowest levels of IFN-γ but higher levels of IL-4. It appears that a proportion of the cells with specificities for early antigens had the Th2 or Th0 phenotype. Our results emphasize that antigens from lung-stage larvae are an important source of potentially protective molecules.