Active and passively induced experimental autoimmune encephalomyelitis in common marmosets: a new model for multiple sclerosis.
A chronic relapsing-remitting form of experimental autoimmune encephalomyelitis was induced in the common marmoset Callithrix jacchus following a single immunization with human white matter. Individual animals in this species are born as natural bone marrow chimeras, allowing transfer of functional T-cell populations between genetically distinct siblings. The acute disease was characterized clinically by mild neurological signs. Pathologically, the disease was characterized by perivascular mononuclear cell infiltrates, large foci of primary demyelination, and reactive astrogliosis. No animal displayed hemorrhagic-necrotic lesions or polymorphonuclear cell infiltrates characteristic of other acute forms of primate experimental autoimmune encephalomyelitis. A late spontaneous relapse occurred in each of 2 animals followed for 3 to 12 months subsequent to recovery from the acute attack. In these animals, chronic lesions consisted of mononuclear cell infiltrates within large sharply defined areas of demyelination and astrogliosis, and resembled active plaques of chronic multiple sclerosis. Proliferative responses to myelin basic protein but not to myelin proteolipid protein were present in peripheral blood lymphocytes of immunized animals. Furthermore, myelin basic protein-reactive T-cell lines derived from immunized donors induced clinical signs of experimental autoimmune encephalomyelitis when adoptively transferred into a sibling, indicating that myelin basic protein-reactive T cells can induce disease in this species. Because of its clinical and pathological similarity to human multiple sclerosis and the ability to adoptively transfer experimental autoimmune encephalomyelitis, this model system should prove useful in the analysis of the immunological mechanisms responsible for autoimmune demyelination in outbred primates.
Massacesi
L
L
Department of Neurology, University of California, San Francisco 94143, USA.
Genain
C P
CP
Lee-Parritz
D
D
Letvin
N L
NL
Canfield
D
D
Hauser
S L
SL
D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology