Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial tissues. A hallmark of the inflammatory process is the accumulation of mononuclear cells in the inflamed synovium. It has become increasingly clear that lymphocytes enter sites of inflammation following specific receptor-mediated binding and transendothelial migration. Whether specific subsets of lymphocytes are uniquely recruited to enter inflammatory sites has not been explored in detail. It is hypothesized that specific lymphocyte populations, exhibiting a distinctive phenotypic and functional capacity, preferentially migrate into sites of inflammation. The proposed studies will utilize in vitro transendothelial migration assays to identify T lymphocytes that express a migratory capacity. The distinguishing characteristics of these lymphocyte subsets will be identified. Further studies will examine the mechanisms mediating transendothelial migration and will examine the functional capacities of these cells as well. In addition to T cells, B cells accumulate in rheumatoid synovial tissue, although the adhesion mechanisms utilized by B cells are not well understood. The proposed studies will examine the adhesion and transendothelial migration of B cells. We will determine whether specific B cell populations express a migratory behavior and whether this can account for the accumulation of B cells in inflammatory sites. The proposed studies will also examine the signals generated in T cells and endothelial cells (EC) following the cell-cell interactions. We will utilize soluble forms of adhesion receptors to delineate the mechanisms induced in T cells and EC which may regulate the transendothelial migration of T cells. Finally, the proposed studies will characterize in detail the migratory behavior of lymphocytes isolated from RA patients and compare it with that of normals. The proposed research should provide a comprehensive view of the mechanisms governing migration of T and B lymphocytes into rheumatoid synovium, and should provide information concerning the hypothesis that migratory capacity accounts for the cells found in the inflammatory tissue.
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