Study of T-cell parameters in Rheumatoid Arthritis

Abstract

T-cells play an important role in the pathogenesis of rheumatoid arthritis (RA). So far, the contribution of T-lymphocytes to the disease course, as well as the characteristics of the (auto)antigens involved in the activation of these immune-competent cells are not yet completely understood. This study is aimed to further characterize the pathogenic T-cell response in the autoimmune response observed in the affected joints of RA patients. We will study T-cells in early and chronic RA patients and compare TCR V gene expression profiles in peripheral blood and synovial cavity samples. In addition, TCR V gene profile changes will be studied over time. TCR V gene analysis will thus be the central subject of the thesis. So far, TCR V gene studies yielded inconclusive results. Genetic and clinical heterogeneity of the study group, the inclusion of depleted or non-depleted in vivo stimulated or non-stimulated T-cells and the variability in technological procedures applied, may all explain the observed differences. To exclude in vitro manipulations that could affect the in vivo situation, we studied unstimulated freshly isolated mononuclear cells from peripheral blood, synovial fluid and/or synovial tissue samples. TCR V gene expression profiles and clonal characteristics were determined.