title: Severe combined immunodeficiency disease: a model of T-cell dysfunction.
abstract: Studies in three patients with severe combined immunodeficiency disease (SCID) and normal adenosine deaminase demonstrated that the combined defect of both T- and B-lymphocyte function may reflect the lack of normal maturation of thymic epithelial cells. This results in the failure of initiation of T-cell differentiation and consequent failure of T-cell dependent maturation of B-lymphocytes to an antibody-secreting stage. SCID B lymphocytes were shown to be capable of generating a specific IgM-antibody response to two T-cell-dependent antigens in vitro under either of the following conditions: (a) provision of autologous T-helper cells which were induced following incubation of precursor cells on monolayers of cultured human thymic epithelium or (b) in the presence of allogeneic T-helper cells. Specific IgM anti-ovalbumin (OA) responses were also generated in the absence of provided T-helper cells when the antigen was insolubilized (Sepharose-OA). The antibody-secreting cells and their circulating precursors carried surface IgM, HLA and Ia-like determinants and proliferated in response to antigen. Identification of this form of SCID may be important when considering therapy and provides an excellent model for the study of the T-cell-dependent acquisition and expression of B-cell immunity.
mesh_terms: D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004847:Epithelial Cells; D006462:Hemolytic Plaque Technique; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D008211:Lymphocyte Cooperation; D008954:Models, Biological; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology