EFFECT OF DISEASE STAGE ON CLINICAL OUTCOME AFTER SYNGENEIC BONE-MARROW TRANSPLANTATION FOR RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Relapsing experimental autoimmune encephalomyelitis (R-EAE) is an immu ne-mediated demyelinating central nervous system (CNS) disease. Myeloa blation and syngeneic bone marrow transplantation (SBMT), when perform ed at the peak of acute disease (day 14), prevented glial scarring and ameliorated the disease severity. In contrast, when syngeneic BMT was performed late in chronic phase (day 78), significant glial scarring remained and the clinical severity did not differ significantly from t hat of the controls. After SBMT in either the acute or chronic phase o f disease, the posttransplant immune system remained responsive to mye lin epitopes as determined by in vitro proliferation and interferon-ga mma (IFN-gamma) production. However, in mice undergoing SBMT, in vivo delayed-type hypersensitivity (DTH) responses were significantly decre ased while IFN-gamma RNA levels and inflammatory infiltrates: within t he CNS were slightly improved. We conclude that failure of SBMT to imp rove the clinical disease when performed in chronic phase may be due t o preexisting glial scarring. We also conclude that in the absence of glial scarring and irreversible neuronal injury, in vivo DTH responses and histology are better predictors of clinical improvement than in v itro proliferation or IFN-gamma cytokine production. (C) 1998 by The A merican Society of Hematology.