ABSTRACT—In primary biliary cirrhosis (PBC) enhanced lymphocyte cytotoxicity, disruption by mononuclear cells of intrahepatic bile ducts, as well as high levels of circulating autoantibodies, immunoglobulins and immune complexes are found. These observations suggest the presence in PBC of defective regulation of immune functions. To evaluate immune regulation of T‐cell and B‐cell function in PBC, we measured the capability of suppressor cells generated by concanavalin A (Con A) from peripheral blood mononuclear cells (PBMC) to inhibit allogeneic T‐cell proliferative responses as well as B‐cell immunoglobulin synthesisin vitro.The inhibitory effect of Con A‐induced suppressor cells on T‐cell proliferation was significantly reduced in PBC patients compared to controls. This immunoregulatory defect did not correlate with indicators of disease activity and was not seen in patients with chronic extrahepatic biliary obstruction. In contrast, Con A‐induced suppressor cells from PBC patients inhibitedin vitroIgG and IgM synthesis normally. Finding that the potential to generate suppressor cell activity of B‐cell immunoglobulin synthesis was preserved in PBC, we explored other mechanisms for elevated globulins in this disease. Comparingin vitroimmunoglobulin synthesis by unstimulated and pokeweed mitogen‐stimulated PBMC from PBC patients and controls, we found that baseline IgG synthesisin vitrowas normal but baseline IgM synthesis significantly depressed in PBC. On the other hand, whereas PBMC from PBC patients responded normally to pokeweed mitogen stimulation of IgM synthesis, the same PBMC were refractory to pokeweed mitogen stimulation of IgG synthesisin vitro.These studies suggest that in PBC there is a dissociation between inducible suppressor cell activity of T‐cell function, which is impaired, and inducible suppressor cell activity of B‐cell immunoglobulin synthesis, which is preserved. Whereas a defect in regulation of cellular immune function may provide a permissive environment for initiation or perpetuation of cell‐mediated autoimmune hepatobiliary injury in PBC, our studies failed to identify an extrinsic immunoregulatory defect to account for humoral immune aberrations, which may result, instead, from altered responsiveness in
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