Immunologic Unresponsiveness, Immunity and Enhancement in Experimental Allergic Encephalomyelitis

Abstract

Progressive and fatal experimental allergic encephalomyelitis (EAE) in guinea pigs was accompanied by the development of delayed hypersensitivity and low-titered ciruclating antibody to central nervous system (CNS) antigens. Inoculation with cyclophosphamide and allogeneic CNS tissue suspension produced a long-lasting immunologic unresponsiveness in which subsequent lethal challenge with allogeneic CNS tissue did not produce disease and related immunologic responses. Delayed hypersensitivity to allogeneic CNS antigens could not be demonstrated. Only partial suppression of EAE, accompanied by the development of delayed hypersensitivity and high-titered circulating antibodies, followed challenge of such unresponsive guinea pigs with xenogeneic (rabbit or dog) CNS tissue. Similar inoculation of allogeneic or xenogeneic CNS suspension, but without cyclophosphamide, produced immunity to subsequent lethal challenge. Both delayed hypersensitivity and high-titered 7 S, γ2 complement-fixing antibodies were then present. Passive transfer of such high-titered allogeneic antibody partially protected normal recipients against lethal challenge, whereas sera from immunologically unresponsive animals or from animals with antibodies to xenogeneic CNS tissue were ineffective. After active challenge with allogeneic CNS tissue, guinea pigs which had also received sera from paralyzed, dying animals developed more severe disease and died at a faster rate than control animals.