title: Evidence that defective gamma interferon production in patients with primary immunodeficiencies is due to intrinsic incompetence of lymphocytes.
abstract: We have selected 11 patients with primary immunodeficiency disorders predominantly affecting T lymphocyte function (four with ataxia-telangiectasia (AT), four with common variable immunodeficiency (CVI) and one each with Wiskott-Aldrich syndrome, hyper-IgE syndrome and combined immunodeficiency) with defective gamma interferon (IFN-gamma) production in vitro. Induction with phytohaemagglutinin showed low interleukin 2 (IL-2) production concomitant with reduced IFN-gamma titres. However the addition of 10 U/ml of rIL-2 to cultures stimulated with staphylococcal enterotoxin B or galactose oxidase failed to restore IFN-gamma production in defective cases. IFN-gamma was titrated by both bioassay and immunoradiometric assay, ruling out the possible release of inactive or altered IFN-gamma molecules. Normal levels of IFN-gamma were found in patients of patients with AT, as well as in two AT and two CVI cases, demonstrating heterogeneity of defects within these syndromes. Soluble inhibitors or cellular suppression of IFN-gamma were not observed in mixing experiments. The possibility that defective interaction between accessory cells and T lymphocytes might account for the poor response to the inducing agents was ruled out as no IFN-gamma was produced using a calcium ionophore--which bypasses this step--in seven patients with absolute IFN-gamma deficiency.
mesh_terms: D001260:Ataxia Telangiectasia / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology
chemical_list: D007376:Interleukin-2; D010835:Phytohemagglutinins; D000001:Calcimycin; D007371:Interferon-gamma