Demyelination following transfer of human lymphocytes into mice with severe combined immunodeficiency

Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease in humans. We investigated adoptive transfer of demyelinating lesions into severe combined immunodeficiency (SCID) mice via injection of peripheral blood lymphocytes (PBLs) from MS patients. PBLs from chronic progressive MS patients were injected 2-7 times at monthly intervals into 8-week-old or newborn SCID mice (n = 51). Immunocompetent mice (n = 10) were injected with similar PBLs from MS patients. Other SCID mice (n = 17) were injected with PBLs obtained from healthy human donors. Mice were sacrificed (2-8 weeks after the last injection); brains and spinal cords were studied with HE and myelin stains, and lymphocytic markers. Demyelinating lesions occurred in 2 mice injected with MS lymphocytes and in one mouse injected with cells from a healthy donor. In addition, occasional meningitis, hydrocephalus, periventricular leukomalacia, lymphomas of either mouse or human origin, and splenomegaly occurred in some mice. Thus transfer of PBLs from MS patients or normal controls can occasionally produce inflammatory demyelinating lesions in SCID mice. This phenomenon which does not appear to be specific to MS lymphocytes may be explained by 'graft-versus-host' of the human lymphocytes against the mouse tissue.