ANTIGENS DERIVED FROM LUNG-STAGE LARVAE OF SCHISTOSOMA-MANSONI ARE EFFICIENT STIMULATORS OF PROLIFERATION AND GAMMA-INTERFERON SECRETION BYLYMPHOCYTES FROM MICE VACCINATED WITH ATTENUATED LARVAE

Protective immunity in C57BL/6 mice exposed to optimally irradiated la rvae of Schistosoma mansoni operates against challenge parasites in th e lungs and is dependent upon T-helper 1 (Th1) lymphocytes which secre te abundant gamma interferon (IFN-gamma). As an initial step in the id entification of the molecules which mediate this immunity, antigenic m aterials released by larvae at various times during in vitro culture w ere compared for the ability to induce proliferation of lymph node cel ls recovered from mice 4 to 6 days after exposure to attenuated parasi tes, Cells from mice vaccinated with cercariae proliferated most stron gly to larval antigens released soon after transformation. In contrast , cells from mice immunized with lung-stage schistosomula responded po orly 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 betwee n IFN-gamma and interleukin-4 (IL-4) secretion depended on the source of antigen used for restimulation. Thus, material released between day s 6 and 8 by in vitro-cultured larvae, and the soluble extracts of who le lung-stage larvae, induced abundant IFN-gamma but little IL-4. This finding implies that an overwhelming proportion of the lymphocytes re sponsive to lung-stage antigens had the Thl phenotype, In contrast, an tigens from cercariae and skin-stage larvae induced the lowest levels of IFN-gamma but higher levels of IL-4. It appears that a proportion o f the cells with specificities for early antigens had the Th2 or Th0 p henotype. Our results emphasize that antigens from lung-stage larvae a re an important source of potentially protective molecules.