The studies in this proposal are designed to answer the question of whether the T lymphocytes found within the synovium of patients with rheumatoid arthritis (RA) and Lyme arthritis have a restricted repertoire of T cell receptors (TCR). This question is fundamental to our understanding of the pathogenesis of RA and Lyme arthritis. The central hypothesis to be tested is that synovial tissue in these two diseases contain populations of T lymphocytes which share TCR gene elements, thus identifying cells which express a restricted TCR repertoire. If such T cells are identified, it is likely that they will be specific for antigens that induce or perpetuate the synovitis. T cells will be cloned immediately from synovial tissue, eliminating the potential for expansion of selected cells. The diversity of the synovial tissue T cell clones will be determined by comparing Southern blots of their T cell receptor (TCR) gene patterns. Cells with identical TCR rearrangements have arisen in situ from the same clone or possibly migrated to the synovium independently, while those with different patterns represent unique clones. To further define relationships between the T cell clones we will determine if there is restricted usage of V-beta region TCR genes with V region probes that define subfamilies. The restricted usage of V region genes will be determined by Southern blots and by a T cell clone dot blot assay which can be performed on as few as 200 cells. The study of both RA and Lyme arthritis allows us to compare two diseases with similar pathologic changes, but distinct etiologies. Borrelia burgdorferi, the etiologic agent in Lyme disease, is a possible source of the antigens responsible for the inflammatory synovitis. B. burgdorferi-specific lines and clones will be developed and the TCR rearrangements of these antigen specific cells compared to the whole T cell population. Analysis of the TCR of the IL-2 responsive cells from RA and Lyme synovium may identify an activated T cell subset that expresses a restricted repertoire.
| Cooper, S M; Roessner, K D; Naito-Hoopes, M et al. (1994) Increased usage of V beta 2 and V beta 6 in rheumatoid synovial fluid T cells. Arthritis Rheum 37:1627-36 |
| Roessner, K; Fikrig, E; Russell, J Q et al. (1994) Prominent T lymphocyte response to Borrelia burgdorferi from peripheral blood of unexposed donors. Eur J Immunol 24:320-4 |
| Cooper, S M; Dier, D L; Roessner, K D et al. (1991) Diversity of rheumatoid synovial tissue T cells by T cell receptor analysis. Oligoclonal expansion in interleukin-2-responsive cells. Arthritis Rheum 34:537-46 |
