IL-12 ELIMINATES THE TH-2 DEPENDENT PROTECTIVE IMMUNE-RESPONSE OF MICE TO LARVAL STRONGYLOIDES-STERCORALIS

The goal of the present study was to determine if immune-mediated kill ing of S. stercoralis L3 in mice could be modulated by shifting from a Th-2 to a Th-1 type immune response. L3 killing in immunized mice was ablated in CD4(+) T cell-depleted animals, but not in CD8(+) T cell-d epleted or beta 2-microglobulin-deficient mice. Treatment of immunized mice with IL-4 or IL-5 neutralizing MoAb significantly reduced the pr otective effects of vaccination against S. stercoralis, while protecti ve immunity was unimpaired in IFN-gamma knockout mice. Recombinant IL- 12 was administered to infected mice to switch the immume response fro m a Th-2 to a Th-1 type response. Protective immunity was ablated in i mmunized mice that received IL-12 therapy. Eosinophil numbers, eosinop hil peroxidase levels, and parasite-specific IgGI levels were lowered in IL-12 treated immuninized animals, and parasite-specific IgG2a leve ls were increased in these animals. The data indicate that eosinophils are important as mediators of larval killing, and that the establishm ent of Th-2 type immunity results in killing of infective S. stercoral is L3, while a shift to Th-1 type immunity abrogates protective respon ses.