5.6 T-cell receptor expression in patients with rheumatic diseases

Abstract

T -cells playa predominant role in the pathogenesis of rheumatic auto-immune disorders. This is best illustrated in experimental models such as adjuvant arthritis, in which the disease can be transferred by inoculation of healthy animals with T-cell lines taken from affected animals (HOLOSHITZ et al. 1983). In human rheumatoid arthritis, the pathogenic role of T -cells is suggested by their presence in close contact with activated macrophages in the inflamed synovial tissue and by the fact that therapies which cause aT-cell immunodepression may lead to remission of disease activity. On condition that the pathogenic T-Iymphocytes and their respective antigenreceptors (T-cell receptors or TCR) are isolated and well characterized, they can be used effectively in the prevention and treatment of T-cell mediated auto-immune disorders. They may indeed serve as specific targets for immuno therapy (passive vaccination with anti-TCR antibodies) or as tools (active vaccination with attenuated T-cell lines or with synthetic idiotypic peptide) (COHEN 1989; VANDENBARK et al. 1989). This has been shown and repeatedly confirmed in different animal models and in different laboratories. Specific anti-TCR therapy has hitherno been unsuccessful in human rheumatic auto-immune diseases, mainly because the pathogenesis of these diseases is still unclear. In fact, we do not know which antigen induces the auto-immune response and which T-Iymphocytes predominate in this pathogenic process. Our study was designed to analyze TCR expression by lymphocytes derived from inflammatory lesions in different rheumatic conditions. Because of their origin (site of inflammation), we assumed them to be involved in the pathogenesis of the disease (guilt by association). Even if the antigen-reactivity of these cells remains unknown, they may be possible candidates for immune targeting.