THE ROLE OF T-CELLS IN RHEUMATOID-ARTHRITIS

The most striking arguments in favor of a T cell dependent nature of R A are the strong association of the disease with selected class II HLA haplotypes (the ''shared epitope'' hypothesis) and the fact that, in experimental animal models such as adjuvant arthritis, the disease can be transferred by isolated T cell lines. It is true that T cell activ ation at the site of inflammation is not excessive. However, there is now unequivocal evidence for focal synthesis of IL-2 and IFN-gamma in the RA synovial membrane and one may realise that a limited but specif ic T cell activation may be sufficient to induce or perpetuate the imm une process, This same argument may explain the lack of clear TCR rest riction at the sites of inflammation. Untill now no antigen has been d emonstrated to initiate and/or perpetuate RA. Different antigens thoug h have been incriminated in the pathogenesis of RA, including cartilag e antigens (collagen, proteoglycans, chondrocyte antigens), heat shock proteins or exogenous (viral/bacterial) antigens. Unless one can pick up the right antigen and clone the relevant T cells, it will be very hard to directly prove a T cell-dependent nature of the disease.