NOVEL ADJUVANTS FOR INDUCTION OF T-CELL AND ANTIBODY-RESPONSES TO ENCEPHALITOGENIC AND REGULATORY DETERMINANTS IN LEWIS RATS

Treatment of human autoimmune diseases may be enhanced by using adjuva nts that can selectively induce immunoregulatory responses. Two versio ns of a novel nonionic block copolymer adjuvant suitable for human use , Optivax Oil Formulation (OF) and Optivax Aqueous Formulation (AF), w ere evaluated for induction of immunity to encephalitogenic and regula tory T-cell receptor (TCR) V-gene determinants. In Lewis mrs immunized with myelin basic protein (BP), Optivax OF was more efficient than Op tivax AF for inducing delayed type hypersensitivity (DTH), T-cell prol iferation, antibodies, and even mild clinical signs of experimental au toimmune encephalomyelitis (EAE). Similarly Optivax OF was more effici ent for inducing inflammatory T-cell and antibody responses to immunor egulatory V beta 8.2 proteins and peptides than Optivax AF which induc ed a noninflammatory Th2 response. In general DTH response to the vari ous immunogens was reflected by increased cellularity and mRNA levels for IFN-gamma, in draining lymph nodes, whereas LN cell proliferation without DTH was characterized by increased IL-2 mRNA levels but low or absent IFN-gamma message. These data suggest important differential a djuvant effects of Optivax OF versus Optivax AF on the respective indu ction of Th1 versus Th2 responses that may be useful in the selective treatment of human immune disorders. (C) 1997 published by Elsevier Sc ience Ltd.