Effective antigen-specific immunotherapy in the marmoset model of multiple sclerosis.
Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease. CNS lesions were also reduced as assessed in vivo by magnetic resonance imaging. Thus, specific Ag-directed therapy can be effective and nontoxic in primates.
McFarland
H I
HI
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lobito
A A
AA
Johnson
M M
MM
Palardy
G R
GR
Yee
C S
CS
Jordan
E K
EK
Frank
J A
JA
Tresser
N
N
Genain
C P
CP
Mueller
J P
JP
Matis
L A
LA
Lenardo
M J
MJ
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001921:Brain / Q000473:pathology; D002144:Callithrix / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods*; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D016207:Cytokines; D016056:Immunodominant Epitopes; D007166:Immunosuppressive Agents; C101821:MP4 protein, chimeric; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D011993:Recombinant Fusion Proteins