The role of T-cells in rheumatoid arthritis and the use of immunomodulating drugs.
Rheumatoid arthritis (RA) is a chronic inflammatory process of unknown etiology affecting 1% of the population worldwide. It results in excess morbidity in a majority of cases and early mortality in patients with aggressive disease. Early immunohistologic studies of the rheumatoid synovium demonstrate that T-cells, especially cluster of differentiation (CD)4(+) cells, are a major component of the infiltrating inflammatory cells. It has also been demonstrated that RA patients share a common major histocompatibility complex (MHC) class II molecule, HLA-DR4. Immune activation by T-cells requires the formation of the antigen recognition complex composed of the T-cell receptor, the MHC II molecule, and antigen. Many treatment modalities for RA have targeted the T-cell and/or the antigen recognition complex. These have varied from relatively crude methods such as leukopheresis to very specific monoclonal antibodies directed toward specific T-cell antigens such as the CD4 molecule itself. Not only have these therapies been effective, but also they have provided some interesting data on the pathogenesis of RA. Unfortunately, some have been associated with harmful side effects. To date, the safest and most effective modality has been immunomodulatory drugs such as cyclosporin and FK506, either alone or in combination with other agents. It appears that the earlier these treatments are started in the course of RA, the more effective they are, not only in controlling disease but also in achieving a potential remission.
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Arizona Health Sciences Center, University of Arizona, Tucson, Arizona 95724, USA.