Polymerase chain reaction (PCR) technology has been used to determine the relative utilization of T cell receptor (TCR) variable (V) region gene families in T cell populations, including those residing in sites of inflammation. In particular, a number of approaches to identify potentially pathogenic T cells in patients with rheumatoid arthritis (RA) are presented. It is hypothesized that the TCR repertoire of the T cells which are driving the autoimmune response, in the peripheral blood or in the synovial membranes, may be limited. Pathogenic T cells responding to an autoantigen are likely to be CD4+ memory cells and bear cell surface markers indicative of current or past activation, such as CD45RO or the IL-2 receptor. We intend to determine whether these cells utilize a limited number of TCR V gene families. We will also investigate a model of T cell-endothelial cell interaction where T cells capable of migrating through an endothelial cell monolayer are compared to nonadherent T cells. The migrating cells are enriched for a subset of memory cells. This technique, will be useful for the isolation of this subpopulation from the peripheral blood of RA patients. Biased expression of particular V gene families in T cells implicated by any of these methods may correlate with HLA-DR haplotypes, or with disease activity. The proposed research will contribute to our knowledge both of the participation of T cells in RA, and of the TCR V gene utilization by T cell subpopulations differentiated by function.
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| Jenkins, R N; Nikaein, A; Zimmermann, A et al. (1993) T cell receptor V beta gene bias in rheumatoid arthritis. J Clin Invest 92:2688-701 |
