Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis.
Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis.
McFarland
H I
HI
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Lobito
A A
AA
Johnson
M M
MM
Nyswaner
J T
JT
Frank
J A
JA
Palardy
G R
GR
Tresser
N
N
Genain
C P
CP
Mueller
J P
JP
Matis
L A
LA
Lenardo
M J
MJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D002144:Callithrix; D003711:Demyelinating Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology*; D007271:Injections, Intradermal; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology