Larvae of cestode parasites cause disease in man and domestic animals. In man the larvae of Taenia solium often invade the central nervous system and cause a disease known as neurocysticercosis which has numerous neurological complications including blindness, dementia, convulsions and, not infrequently, death. The infection is characterized by an inefficient and inconsistent cellular immune response but often an intense humoral immune response. It has been shown in several taeniid parasite-host relationships that immune responses are suppressed. In recent experiments we have demonstrated that larvae of Taenia crassiceps in BALB/c mice induce immunosuppression of Th1-like responses, which one would expect to be involved in anti-larval cellular responses; Th2 responses are relatively unaffected. It was also determined that these larvae secrete a glycoprotein of 175 Kd (gp175), consisting of peptide subunits of 68 and 55/52 kDa, which selectively downregulates Th1 responses. Earlier we described similar secreted molecules by larvae of T. solium in patients with neurocysticercosis but did not determine their biological effects. Recent experiments have shown that gpl75 suppresses the ability of human peripheral blood lymphocytes to respond to stimulation with phytohemagglutinin. In the present proposal we are requesting support to continue the studies on the biological role of gpl75 by determining its activities in downregulating both the induction and expression of immune responses, the effects of neutralizing gpl75 on growth and development of larvae in vivo, and to clone the genes and produce recombinant subunit peptides in order to more readily determine the immunoregulatory activity of this parasite- derived immunosuppressive molecule.
