Reversal of spontaneous progressive autoimmune encephalomyelitis by myelinbasic protein-induced clonal deletion

Autoimmune encephalomyelitis can be initiated spontaneously and developed p rogressively in TCR transgenic mice specific for myelin basic protein when exposed to non-sterile environment, thus more closely mimicking human multi ple sclerosis, By intravenous administration of myelin basic protein, we su cceeded in reversing the clinical and pathological signs of progressive spo ntaneous disease in these mice. Flow cytometry showed that the majority of transgenic T cells in lymph nodes and spleen as well as spinal cords of tre ated mice were deleted, Dramatically increased numbers of apoptotic cells m ere found in peripheral immune organs of treated animals. Proliferative res ponses of single transgenic T cell to autoantigen mere significantly decrea sed in treated mice, indicating that the remaining T cells mere anergic, Mo reover, production of both Th1 and Th2 cytokines was suppressed. This study is the first demonstration of reversal of progressive, spontaneous autoimm une disease of the central nervous system, and provides direct evidence tha t apoptosis-induced clonal deletion, along with anergy of remaining cells, but not Th2 switch, play a major part in the reversal of this disease by in travenous administration of autoantigen.