Relapsing
experimental autoimmune encephalomyelitis (R-EAE) is an immune-mediated demyelinating central nervous system (
CNS) disease. Myeloablation and syngeneic
bone marrow transplantation (SBMT), when performed 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 that of the controls. After SBMT in either the acute or chronic phase of disease, the posttransplant immune system remained responsive to myelin
epitopes as determined by in vitro proliferation and
interferon-gamma (IFN-gamma) production. However, in mice undergoing SBMT, in vivo delayed-type
hypersensitivity (DTH) responses were significantly decreased while IFN-gamma
RNA levels and inflammatory infiltrates within the CNS were slightly improved. We conclude that failure of SBMT to improve the clinical disease when performed in chronic phase may be due to 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 vitro proliferation or IFN-gamma
cytokine production.