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.