thymosin and Agammaglobulinemia

Topics: Adenosine Deaminase; Agammaglobulinemia; Bone Marrow Cells; Bone Marrow Transplantation; Cell Differentiation; Chromosome Mapping; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; HLA Antigens; Humans; Immunologic Deficiency Syndromes; Liver Transplantation; T-Lymphocytes; Thymosin; Thymus Gland; Transfer Factor; Transplantation, Homologous; Wiskott-Aldrich Syndrome

Congenitally athymic nude mice (nu/nu) are presented as a model for the study of cell-mediated immunologic deficiencies. These mice possess a vestigial thymus which is incapable of producing mature T-cells as shown by a decreased lymphocyte population carrying the theta antigen and depleted 'thymus-dependent' areas in their peripheral lymphoid organs. However, they have T-cell precursors in their bone marrow. Nude mice lack 'thymosin', a thymic factor secreted by the epithelial cells of the thymus. They also have impaired T-cell functions as demonstrated by an absence of delayed hypersensitivity reactions, an inability to reject skin allografts and a decreased antibody response to some T-dependent antigens. But their response to T-independent antigens is normal. The presence of circulating auto-antibodies and immune-complex type glomerulonephritis in nude mice reinforces the hypothesis that spontaneous autoimmunity and B-cell hyperactivity are associated with T-cell deficiency. On the other hand, they are not especially susceptible to spontaneous tumor development. Correlations are made between the pathologic findings in nude mice and some congenital cellular immunologic disorders in man.

Topics: Agammaglobulinemia; Animals; Antigens; Ataxia Telangiectasia; Autoantibodies; Disease Models, Animal; Graft Rejection; Immunity, Cellular; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Spleen; Syndrome; T-Lymphocytes; Thymosin; Thymus Gland; Wiskott-Aldrich Syndrome

Topics: Agammaglobulinemia; Cells, Cultured; Fetus; Humans; Immunoglobulins; Infant; Spleen; T-Lymphocytes; Thymosin

We have studied two patients with common variable immunodeficiency (CVID), impaired cell-mediated immunity, and high percentages of monocytes in their peripheral blood. Removal of monocytes from cultures of peripheral blood mononuclear cells from both patients increased the in vitro responses to phytohaemagglutinin (PHA) and concanavalin A (Con A) but not to purified protein derivative (PPD), as measured by [3H]thymidine uptake. Similarly, supernatants of monocyte cultures from both patients, unlike supernatants of normal monocytes, suppressed the in vitro responses to PHA and Con A but enhanced the response to PPD by cultured mononuclear cells from the patients and from normal donors. Addition of unfractionated mononuclear cells from both patients to normal mononuclear cells suppressed both pokeweed mitogen (PWM) stimulation and IgG production; this effect was abrogated by removal of monocytes from the patients' mononuclear cell populations. This effect of thymosin on both patients' mononuclear cells was assayed in vitro. Thymosin was ineffective in vitro with cells from the first patient; for the other patient, [3H]thymidine uptake by mononuclear cells stimulated with PPD increased, whereas uptake by Con A-stimulated cells decreased, as did the percentage of E rosette-forming cells, providing further evidence of heterogeneity of the CVID syndrome. The effects of thymosin were also dependent on monocytes.

Topics: Adult; Agammaglobulinemia; B-Lymphocytes; Cell Adhesion; Cell Separation; Chemotaxis, Leukocyte; Humans; Immunity, Cellular; Immunoglobulin G; Lymphocyte Activation; Male; Monocytes; Phagocytes; Rosette Formation; T-Lymphocytes; Thymidine; Thymosin; Thymus Hormones

Topics: Adolescent; Agammaglobulinemia; Ataxia Telangiectasia; Burkitt Lymphoma; Candidiasis, Cutaneous; Child; Child, Preschool; Chronic Disease; Female; Humans; Immunologic Deficiency Syndromes; Lymphatic Diseases; Male; Middle Aged; Syndrome; T-Lymphocytes; Thymosin; Thymus Gland; Thymus Hormones

Topics: Adult; Agammaglobulinemia; Ataxia Telangiectasia; Child; Dose-Response Relationship, Drug; Female; Histocompatibility Antigens; Humans; Immune Adherence Reaction; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes; Infant; Liver; Mosaicism; Nasopharyngeal Neoplasms; Parathyroid Glands; Respiratory Tract Infections; Spleen; Syndrome; T-Lymphocytes; Thymosin; Thymus Extracts; Thymus Gland; Tissue Extracts; Transplantation, Homologous; Wiskott-Aldrich Syndrome