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Defective immunoregulation in primary biliary cirrhosis: CD4+, Leu–8+ T cells have abnormal activation and suppressor function in vitro

To determine whether abnormalities of lymphocyte function in primary biliary cirrhosis are due to altered function of immunoregulatory T cell subpopulations, phenotypic and functional characteristics of CD4+ T cells were examined. The proportion of CD4+ T cells expressing the Leu‐8 and CD45R antigens was normal in patients with primary biliary cirrhosis. The capacity of CD4+, Leu‐8‐T cells to provide helper function for pokeweed mitogen‐stimulated immunoglobulin synthesis by B cells in vitro was similar in patients and controls. However, in contrast to normal individuals and patients with other liver diseases, CD4+, Leu‐8+ T cells from six of 10 patients with primary biliary cirrhosis did not suppress, but enhanced immunoglobulin synthesis. Whereas treatment of CD4+ T cells from normal individuals with anti‐Leu‐8 monoclonal antibody enhanced their suppressor function, similar treatment of CD4+ T cells from patients with primary biliary cirrhosis did not increase their suppressor function. To determine whether the abnormal regulatory function of CD4+, Leu‐8+ T cells was due to a defect of cell activation, the proliferative response of CD4+ T cell subpopulations to mitogenic stimulation was examined. The proliferative responses of CD4+, Leu‐8‐T cells from patients with primary biliary cirrhosis and controls were similar, but the proliferative responses of CD4+, Leu‐8+ T cells from patients with primary biliary cirrhosis were lower than those of control cells. Since the CD4+, Leu‐8+ T cell population plays a role in suppressing immunoglobulin synthesis and is contained within the autoreactive T cell population, the abnormal function of this T cell subpopulation in some patients with primary biliary cirrhosis may play a role in defective immunoregulation found in this disease.