Immunotherapy in rheumatoid arthritis: a review

The starting mode of the pathological process in rheumatoid arthritis (RA) is the presentation of an unknown 'rheumatoid' antigen by an antigen presenting cell to the receptor on the CD4+ T cell. The activation of the CD4+ T cell, and consequently of the cytokine network, is the second step in the inflammatory process. Immunosuppression in RA, obtained using either immunosuppressive drugs (azathioprine, cyclophosphamide, methotrexate), or physical procedures (lymphoapheresis, total lymphoid irradiation) acts specifically on all lymphocyte populations, and can induce a number of side effects, such as myelotoxicity and opportunistic infections. Two promising new therapeutic approaches are being developed, one aimed at specifically reducing the proliferation of activated T cell clones, and the second designed to modulate the activity of the cytokines involved in the inflammatory process. Encouraging results have been so far obtained with: a) cyclosporine A, a somewhat more specific immunosuppressive agent; b) monoclonal antibodies against surface antigens (CD4, CD5, CD7, CD25, CD54) expressed on activated T cells; c) T cell vaccination; and finally (i.v.) recombinant cytokines, their agonists or antagonists. Besides their utility in the treatment of the disease, these new therapeutical procedures should also lead to a better understanding of pathological processes in RA.