Antibodies to OX-40 (CD134) can identify and eliminate autoreactive T cells: implications for human autoimmune disease.
Autoantigen-specific CD4+ T cells have been implicated as the causative cell type in: multiple sclerosis, rheumatoid arthritis, autoimmune uveitis, diabetes mellitus, inflammatory bowel disease and graft-versus-host disease. The pathology of a number of experimentally induced autoimmune diseases is also mediated by autoantigen-specific CD4+ T cells. Ideally, treatment of CD4+ T-cell-mediated diseases would eliminate the autoantigen-specific cells, while sparing the remainder of the T-cell repertoire. We have developed an effective therapy that deletes the autoreactive T cells at the site of autoimmune tissue destruction. This approach uses an antibody directed against a cell-surface protein (OX-40, also known as CD134) that is selectively upregulated on activated autoantigen-specific T cells within the inflamed tissue.
Weinberg
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Laboratory of Basic Immunology, Earle A. Chiles Research Institute, Providence Portland Medical Center, OR 97213, USA. weinbera@ohsu.edu
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000628:therapy; D001327:Autoimmune Diseases / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000628:therapy; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D051381:Rats; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7