INTRAVENOUS ANTIGEN ADMINISTRATION AS A THERAPY FOR AUTOIMMUNE DEMYELINATING DISEASE

Experimental allergic encephalomyelitis is a prototypic autoimmune dis ease characterized by central nervous system inflammation and demyelin ation. Previously, we demonstrated that intravenous administration of high doses of myelin basic protein abrogated the clinical and patholog ical signs of experimental allergic encephalomyelitis by causing the d eletion of encephalitogenic, CD4(+), myelin basic protein-specific T c ells through antigen-induced programmed cell death. In the present stu dy, we further characterized the ability of intravenous antigen admini stration to attenuate an immune response by myelin basic protein-react ive encephalitogenic T cells. We demonstrated that multiple injections of myelin basic protein are required to achieve a therapeutic respons e, and that this form of therapy is effective even after prolonged chr onic disease. These studies showed that although interleukin-2-stimula ted cell cycling is an important factor leading to T-cell death, the a dministration of exogenous interleukin-2 with antigen can result in th e aggravation of clinical disease compared to administration of antige n alone. More importantly, administration of myelin basic protein alon e without interleukin-2 was sufficient to reduce autoreactive T cells and clinical disease in experimental autoimmune encephalomyelitis. Our experiments support the rationale for antigen-specific therapy aimed at inducing the programmed death of autoreactive T cells in autoimmune diseases, potentially including the human demyelinating disease multi ple sclerosis.