Consideration of the possibility that T lymphocytes might be central to the pathogenesis of rheumatoid arthritis (RA) first became prominent in the 1980s (1). Only after new approaches became available for understanding the physiology of the T lymphocyte, particularly the generation of monoclonal antibodies that identified the function of important T cell surface structures, was there the development of a hypothesis for the etiology and pathogenesis of RA that placed the T cell at the center of this disease. By the end of the 1980s a substantial body of evidence had accumulated that justified construction of a “T cell paradigm” for RA, and this model has formed the basis for trials of biologic therapies and other novel immunotherapies in the treatment of this disease.

Observations used to support the concept of a central role of T cells in RA are listed in Table 1. Some are undisputed facts, which any comprehensive explanation for the pathogenesis of the disease must take into account. These include the abundance of T lymphocytes in the joint, the distinctive profile of surface markers on synovial T cells compared with peripheral blood, and the increased frequency of specific class I1 major histocompatibility complex (MHC) alleles in RA. Other observations listed in Table 1, however, are more controversial. The important role of T cells in animal models of inflammatory arthritis is of significance only insofar as such models are accurate representations of RA, which remains unproven. Improvement in RA with T cell-