Treatment of relapsing experimental autoimmune encephalomyelitis in rats with allogeneic bone marrow transplantation from a resistant strain.

We previously showed that relapsing experimental autoimmune encephalomyelitis (R-EAE) in BUF rats, a model for multiple sclerosis, responds favorably to treatment with TBI and syngeneic BMT. Relapses of paresis occurred less frequently than in untreated controls, but were not completely prevented. Therefore, we investigated the effect of allogeneic BMT from the resistant WAG rat strain. BUF rats were treated with either high-dose TBI or CY and Bu followed by allogeneic BMT. This treatment induced complete remission, and reduced both the spontaneous and induced relapse rate more efficaciously than syngeneic BMT. Evidence is provided that a subclinical GVHR contributes to the prevention of spontaneous relapses. The almost complete absence of induced relapses likely results from the repopulation by the resistant immune system of the donor, which proved to be functional by responding to immunization with type II collagen. It is thus unlikely that a BMT-related immunodepression contributed to the lower incidence of induced relapses. We propose that allogeneic BMT should be considered for the treatment of severe progressive MS with a poor prognosis.