DEMYELINATION FOLLOWING TRANSFER OF HUMAN-LYMPHOCYTES INTO MICE WITH SEVERE COMBINED IMMUNODEFICIENCY

Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinati ng disease in humans. We investigated adoptive transfer of demyelinati ng lesions into severe combined immunodeficiency (SCID) mice via injec tion of peripheral blood lymphocytes (PBLs) from MS patients. PBLs fro m chronic progressive MS patients were injected 2-7 times at monthly i ntervals into 8-week-old or newborn SCID mice (n = 51). Immunocompeten t mice (n = 10) were injected with similar PBLs from MS patients. Othe r SCID mice (n = 17) were injected with PBLs obtained from healthy hum an donors. Mice were sacrificed (2-8 weeks after the last injection); brains and spinal cords were studied with HE and myelin stains, and ly mphocytic markers. Demyelinating lesions occurred in 2 mice injected w ith MS lymphocytes and in one mouse injected with cells from a healthy donor. in addition, occasional meningitis, hydrocephalus, periventric ular leukomalacia, lymphomas of either mouse or human origin, and sple nomegaly occurred in some mice. Thus transfer of PBLs from MS patients or normal controls can occasionally produce inflammatory demyelinatin g lesions in SCID mice. This phenomenon which does not appear to be sp ecific to MS lymphocytes may be explained by 'graft-versus-host' react ion of the human lymphocytes against the mouse tissue.