Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates autoimmune encephalomyelitis.
The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.
Weinberg
A D
AD
Veterans Affairs Medical Center, Portland, Oregon 97207, USA.
Bourdette
D N
DN
Sullivan
T J
TJ
Lemon
M
M
Wallin
J J
JJ
Maziarz
R
R
Davey
M
M
Palida
F
F
Godfrey
W
W
Engleman
E
E
Fulton
R J
RJ
Offner
H
H
Vandenbark
A A
AA
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002469:Cell Separation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012276:Ricin / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000276:immunology*
D000922:Immunotoxins; D004676:Myelin Basic Protein; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D012276:Ricin