Enhanced autoreactivity of T-lymphocytes in primary sclerosing cholangitis

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Abstract
Primary sclerosing cholangitis is a chronic, cholestatic liver disease in which immune mechanisms are thought to play a role in the pathogenesis. We have determined the frequencies and functional phenotypes of autoreactive T-lymphocytes in peripheral blood specimens from patients with primary sclerosing cholangitis and healthy adults as an indicator of autoreactivity in primary sclerosing cholangitis. We found a significant increase in the percentage of autoreactive suppressor/cytotoxic T-lymphocytes that become activated in the T-, non-T-autologous mixed lymphocyte reaction in primary sclerosing cholangitis patients (p < 0.002). Blastogenesis in autologous mixed lymphocyte reaction cultures from primary sclerosing cholangitis patients was significantly decreased (p < 0.02), and the magnitude of the decrease correlated directly with the percentage of activated suppressor/cytotoxic T-lymphocytes (r = 0.56, p < 0.01). The percentage of autoreactive, suppressor T-lymphocytes was increased in autologous mixed lymphocyte reaction cultures from primary sclerosing cholangitis patients (p < 0.0001); and suppression of mitogen-induced blastogenesis by autologous concanavalin A-treated mononuclear cells was significantly enhanced. These results, which were unrelated to the histologic stage of liver disease and the presence or absence of active colitis, document the presence of an expanded population of T-lymphocytes in the peripheral blood of patients with primary sclerosing cholangitis that became activated on exposure to autologous major histo-compatibility antigens in the autologous mixed lymphocyte reaction. We hypothesize that these autoreactive cells may be a marker or may participate as effector cells in cell-mediated autoimmunity in primary sclerosing cholangitis.