title: Immunoregulation in an isolated 12-year-old boy with congenital severe combined immunodeficiency.
abstract: We report the evaluation of in vitro immunoregulation in a 12-year-old untreated boy with severe combined immunodeficiency (SCID). Severely hypogammaglobulinemic, the patient was incapable of a specific antibody response to either natural substances or administered antigens. Ficoll-Hypaque-isolated peripheral blood mononuclear cells (MNL) from the patient failed to respond to pokeweed mitogen (PWM) with the normal increment in immunoglobulin-secreting cells, as measured by a reverse hemolytic plaque assay. Since the patient was lymphopenic, his MNL were relatively enriched for monocytes (range = 51-81%). Removal of phagocytic cells or the addition of unrelated irradiated helper T lymphocytes resulted in enhanced, but still suboptimal response to PWM, suggesting some intrinsic defect in B lymphocyte function. Co-culture of patient MNL with normal MNL resulted in marked suppression (12% of predicted) of PWM-induced Ig-secreting cells. Suppressor activity was unaffected by prior irradiation of patient MNL, but was substantially reversed (99% of predicted) by removal of his phagocytic cells, whereas the combination of the two procedures further reversed suppression (184% of predicted). The patient's MNL consistently demonstrated subnormal percentages of T3+ and T4+ cells and subnormal to low normal percentages of T8+ cells. These data suggest both an intrinsic defect in B lymphocyte function, and a relative excess of monocytes which could further inhibit Ig secretion by B lymphocytes. Natural killer (NK) cell function was characterized by normal target cell binding by NK cells but severely depressed NK cell cytotoxicity.
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D003602:Cytotoxicity, Immunologic; D005856:Germ-Free Life; D006801:Humans; D007121:Immunocompetence; D007136:Immunoglobulins / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000151:congenital* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007136:Immunoglobulins