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 myel in basic protein (MBP)-specific T cells at the site of inflammation du ring the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cell s within the central nervous system without affecting peripheral T cel ls. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in ameli oration of EAE. Expression of the human OX-40 antigen was also found i n peripheral blood of patients with acute graft-versus-host disease an d the synovia of patients with rheumatoid arthritis during active dise ase. The unique expression of the OX-40 molecule may provide a novel t herapeutic strategy for eliminating autoreactive CD4(+)T. cells that d oes not require prior knowledge of the pathogenic autoantigen.