Modulation of in vitro synthesis of immunoglobulin and the induction of suppressor activity by therapy with intravenous immune globulin

Abstract

Intravenous immune globulin has become an important modality of replacement therapy for children and adults with hypogammaglobulinemia or agammaglobulinemia. It is also evident that intravenous immune globulin is effective in patients with a variety of autoimmune disorders. The present study was undertaken to evaluate the effects of intravenous immune globulin replacement therapy in patients with common variable hypogammaglobulinemia. We measured pokeweed mitogen-induced immunoglobulin synthesis of patients' peripheral blood mononuclear cells cocultured in equal numbers with normal subjects' lymphocytes to assess suppressor cell activity. The mean suppressor cell activity in coculture experiments at baseline of nine patients in the study was − 16%. Suppressor activity was demonstrated in two of nine patients at baseline who received intravenous immune globulin therapy before initiation of the study. After intravenous immune globulin therapy at a low dose (100 to 200 mg/kg/mo), suppressor cell activity was demonstrated in all nine patients, which ranged from −63% to −100%. In five patients intravenous immune globulin therapy was discontinued for 4 months. There was a return to baseline levels, with suppressor activity ranging from −20% to −50%. On reinstitution of high-dose intravenous immune globulin therapy (300 to 400 mg/kg/mo), all patients except one again demonstrated increased suppressor cell activity. Cell separation and recombination cell culture experiments were performed. All patients had an intrinsic B cell defect before the initiation of therapy so that the effects of intravenous immune globulin therapy on B cell function could not be assessed. Combining normal B cells with the patient's T cell-enriched fraction showed marked suppression of pokeweed mitogen-induced immune globulin synthesis. This suppression was reversible by irradiation of the T cell fraction. Removal of CD8-positive T cells by cell sorting resulted in normal immunoglobulin synthesis. These findings suggested that the CD8-positive T cell subset accounted for the increase in suppressor activity in patients with common variable hypogammaglobulinemia receiving intravenous immune globulin therapy.