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  • Title: Mycobacteria and human heat shock protein-specific cytotoxic T lymphocytes in rheumatoid synovial inflammation.
    Author: Li SG, Quayle AJ, Shen Y, Kjeldsen-Kragh J, Oftung F, Gupta RS, Natvig JB, Førre OT.
    Journal: Arthritis Rheum; 1992 Mar; 35(3):270-81. PubMed ID: 1371388.
    Abstract:
    OBJECTIVE: To study the cytotoxic capacity of mycobacteria-specific T lymphocyte lines and clones from sites of inflammation in patients with rheumatoid arthritis (RA). We also studied antigen specificity, surface phenotype, expression of T cell receptors (TCR), and HLA restriction. METHODS: Autologous macrophages (M phi) from the synovial membrane (SM), synovial fluid (SF), or peripheral blood (PB) were used as target cells in cytotoxicity assays. RESULTS: All SM and SF cell lines tested thus far have shown specific lysis of the autologous M phi from SM or PB that had been pulsed with BCG (bacillus Calmette-Guerin), but no cytotoxicity when the targets were pulsed with irrelevant antigens such as tetanus toxoid and Chlamydia. Both CD4+ and CD8+ cells were shown to be involved in the specific cytolysis. The majority of the cytotoxic T lymphocyte (CTL) lines were TCR alpha/beta + cells. However, both TCR alpha/beta + and TCR gamma/delta + clones (TCR delta 1+) from one RA patient showed antigen-specific lysis. Antigen-specific recognition by a number of CTL lines and clones generated from SF and SM was restricted by HLA-DR molecules. Two Mycobacterium bovis 65-kd heat shock protein (HSP)-specific TCR alpha/beta + SF T cell clones also lysed M phi that had been pulsed with a recombinant human 65-kd HSP. CONCLUSION: Joint inflammation and destruction might be partly attributable to a cross-reaction of mycobacteria-induced cytotoxic T cells with self HSP.
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