concanavalin-a and Syndrome

Five Persian Jews were detected with the polyglandular deficiency syndrome (PDS). Primary hypoparathyroidism and hypogonadism were present in each, adrenal insufficiency in two, and insulin-dependent diabetes mellitus and latent hypothyroidism in single subjects. The percentage of T and B cells, and the mononuclear cell response to phytohemagglutinin and Concanavalin A were normal in all five. IgG and IgA levels and the OKT4+/OKT8+ cell ratio were low in one subject. Antinuclear and antithyroid antibodies were present in one subject. HLA-DR5 was present in 4/4, HLA-24 and B5 (B51) in 3/4 subjects. A single case of isolated hypoparathyroidism (IHP) was detected among 12 first degree relatives. HLA antigens B8, DR3, were absent in all of these subjects. Seven non-Iranian Jews with IHP were also examined. HLA A26 or A25 were present in all seven. Persian Jews appear to have a unique variant of PDS.

Topics: Adolescent; Adrenal Insufficiency; Adult; Antibodies, Antinuclear; B-Lymphocytes; Concanavalin A; Diabetes Mellitus, Type 1; Female; HLA Antigens; Humans; Hypogonadism; Hypoparathyroidism; Hypothyroidism; Immunoglobulin A; Immunoglobulin G; Iran; Jews; Lymphocyte Activation; Male; Monocytes; Phytohemagglutinins; Syndrome; T-Lymphocytes

Isoniazid (INH) and hydralazine (HYD) are transglutaminase (TGase, E.C.2.3.2.13.) substrates containing catalytically recruitable hydrazyl groups. Since they can be expected to inhibit TGase-mediated cell functions by competing with physiological substrates, their effect upon allogeneically and lectin-induced proliferation of mononucleocytes and upon zymosan-induced chemiluminescence of phagocytes was studied. Both compounds inhibited chemiluminescence in a dose-dependent manner. ID50 of HYD was consistently below 20 microM, while that of INH was above 120 microM. Proliferation of immunocompetent cells was suppressed by HYD with an ID50 of 60 microM, INH was inhibitory only above 5000 microM. Analogs of both compounds not containing hydrazyl groups proved to be inactive. Control experiments indicated that inhibition is not due to toxicity or lipophilicity of the compounds, structural analogs lacking a hydrazyl moiety were inactive. It is suggested that, in vivo, HYD interferes with signal-induced TGase-dependent leucocyte functions essential for immunologic stability, and that the resultant dysregulation with disruption of self tolerance contributes to the HYD promoted lupus-like syndrome.

Topics: Concanavalin A; Humans; Hydralazine; In Vitro Techniques; Isoniazid; Leukocytes; Luminescent Measurements; Lupus Erythematosus, Systemic; Lymphocyte Activation; Models, Biological; Syndrome; Transglutaminases

The functional properties of cytotoxic lymphocytes from patients with Vogt-Koyanagi-Harada disease ( VKH ) specific for human melanoma cells (P-36 melanoma cell line established from a patient with malignant melanoma) were investigated by using monoclonal antibodies specific for human T cell subsets. Peripheral blood lymphocytes (PBL) from patients with VKH showed significant cytotoxic activity against the P-36 (SK-MEL-28) human melanoma cell line, but not against a human cervical carcinoma of the uterus cell line (HeLa-S3 cell line) or against a mouse melanoma cell line (B-16 cell line) originating from a C57BL/6 strain mouse or against the EL-4 mouse lymphoma cell line from a C57BL/6 mouse. The cytotoxic activity of the patients' PBL against the P-36 melanoma cell line was markedly reduced by pretreatment of the PBL with monoclonal anti-human Leu-1 antibody plus rabbit complement, but it was reduced to much less extent by pretreatment with either monoclonal anti-human Leu-2a or Leu-3a antibody plus rabbit complement. The specific cytotoxic activity of the patients' PBL against the P-36 human melanoma cell line is, therefore, mediated by T cells bearing Leu-1+ Leu-2a+ or Leu-1+ Leu-3a+ antigens. Furthermore, the cytotoxic activity was shown to be blocked not only by anti-Leu-2a antibody specific to human cytotoxic/suppressor T cells but also unexpectedly by anti-Leu-3a antibody which has previously been considered to be specific to human inducer/helper T cells. The results of this study suggest that at least two distinct subpopulations of cytotoxic T cells specific for P-36 human melanoma cells are present in the peripheral blood of VKH patients. These cytotoxic T cells have different surface antigens, Leu-2a and Leu-3a.

Topics: Adult; Animals; Antibodies, Monoclonal; Antigens, Surface; Cell Line; Complement System Proteins; Concanavalin A; Cytotoxicity, Immunologic; Epitopes; Female; HeLa Cells; Humans; Iritis; Killer Cells, Natural; Kinetics; Lymphocytes; Male; Melanocytes; Melanoma; Mice; Mice, Inbred C57BL; Middle Aged; Rabbits; Syndrome; T-Lymphocytes, Cytotoxic; Uveitis

Using peripheral blood lymphocytes from 8 healthy individuals and 5 patients with untreated Graves' disease, direct effects of methimazole (MMI) and propylthiouracil (PTU) on lectin-induced lymphocyte proliferative response were studied. Lymphocytes were cultured for 72 hr in the presence of lectins and antithyroid drugs. Lymphocyte DNA synthesis was counted by incorporation of 3H-thymidine. MMI at 1,000 microM enhanced lectin-induced lymphoproliferation of peripheral blood lymphocytes from both patients with Graves' disease and healthy individuals, at every point of culture time, while PTU showed a tendency toward suppression. These results suggest that this lympho-stimulation by MMI may be a causative factor related to insulin autoimmune syndrome, as deduced from the clinical reports that insulin autoimmune syndrome is, sometimes, found in patients with Graves' disease treated with MMI. This lympho-stimulation was evident regardless of the time of MMI addition, thus indicating that MMI is, by its action, a lymphoid stimulator and may lead to the insulin autoimmune syndrome in predisposed subjects with underlying Graves' disease.

Topics: Autoimmune Diseases; Concanavalin A; Graves Disease; Humans; Insulin Antibodies; Lymphocyte Activation; Methimazole; Phytohemagglutinins; Pokeweed Mitogens; Propylthiouracil; Syndrome

Schwachman's syndrome is characterised by pancreatic insufficiency and frequent infections. Absolute polymorphonuclear leucocyte (PMN) counts are low in many patients, and the PMN show abnormal chemotaxis. It was postulated that a cytoskeletal defect might underlie these abnormalities, and a cytoskeleton-dependent function, the surface distribution and mobility of concanavalin-A receptors, was studied on neutrophils from Schwachman's syndrome patients. Approximately a third of the neutrophils in each patient showed a patched distribution of fluorescein-conjugated concanavalin A (FITC-con A) rather than the usual diffuse staining pattern. These patched neutrophils also bound larger amounts of FITC-con A than diffusely stained or capped PMN from the same patient. Antitubulin treatment did not alter the proportion of patched PMN. These findings suggest that a cytoskeletal defect underlies the patching of FITC-con A on the PMN surface. This defect could also contribute to the abnormal chemotaxis and frequent infections found in Shwachman's syndrome patients.

Topics: Adolescent; Agranulocytosis; Cell Membrane; Chemotaxis; Child, Preschool; Concanavalin A; Cytoskeleton; Disease Susceptibility; Exocrine Pancreatic Insufficiency; Humans; Infections; Neutropenia; Neutrophils; Receptors, Concanavalin A; Staining and Labeling; Syndrome

The status of suppressor T cells (Ts) was assessed in seven children with the hyper IgE syndrome (recurrent staphylococcal infections, eczematous skin rash, and elevated serum IgE) to determine whether a deficiency in Ts is associated with increased IgE synthesis. When circulating T cells and their subsets were enumerated with the aid of monoclonal antibodies that identify T cells (T3), helper/inducer T cells (T4), and suppressor/cytotoxic T cells (T8), there was a selective deficiency of T3+ cells (51.7+/-11.2% vs. 66+/-5% for normal controls) and of T8+ cells (7.5+/-4.4% vs. 22+/-4% for normal controls) but not of T4+ cells (36.5+/-7.5% vs. 37+/-3% for normal controls). Suppressor T cell function was assessed by examining the ability of mononuclear cells incubated for 48 h with concanavalin A to suppress the proliferation of fresh autologous mononuclear cells in response to the mitogens phytohemagglutinin and pokeweed mitogen. All seven patients were severely deficient in concanavalin A-inducible suppressor cells. In vitro de novo synthesis of IgE in 6-d cultures of peripheral blood lymphocytes was measured in four patients by a solid-phase radioimmunoassay. Mononuclear cells from all four patients synthesized spontaneously increased quantities of IgE in vitro (4,950+/-3,760 pg/10(6) cells vs. 250+/-215 pg/10(6) cells for eight normal controls). IgE synthesis was suppressed by the addition of parental T cells to the culture. Elimination of the T8+ subset, but not of the T4+ subset, by complement-dependent lysis resulted in the loss of the capacity of parental T cells to suppress IgE synthesis. These results suggest that a deficiency of Ts underlies the elevated IgE levels observed in the hyper IgE syndrome.

Topics: Adult; Antibodies, Bacterial; Antigens, Bacterial; Child; Child, Preschool; Concanavalin A; Female; Humans; Hypergammaglobulinemia; Immune Tolerance; Immunoglobulin E; Male; Staphylococcus aureus; Syndrome; T-Lymphocytes, Regulatory

Topics: Child; Concanavalin A; Humans; Hypergammaglobulinemia; Immunity; Immunoglobulin E; Lymphocyte Activation; Male; Phagocytosis; Phytohemagglutinins; Pokeweed Mitogens; Syndrome

A patient with Sézary syndrome developed a diffuse undifferentiated lymphoma of T-cell origin. After becoming resistant to multiple chemotherapeutic agents, the patient was treated with antithymocyte globulin. A 75% reduction in adenopathy and complete resolution of skin erythema was observed during an 8-day period. In addition the percent of circulating T cells and the ability of those cells to respond to phytohemagglutinin and concanavalin A were reduced after antithymocyte globulin therapy. The patient died of an intracerebral hemorrhage secondary to profound thrombocytopenia. The study suggests that tumor lysis may be achieved by passive antibody therapy in certain advanced lymphomas.

Topics: Antilymphocyte Serum; Concanavalin A; Dermatitis, Exfoliative; Humans; Immunotherapy; Keratoderma, Palmoplantar; Lectins; Lymphatic Diseases; Lymphocyte Activation; Lymphoma; Male; Middle Aged; Syndrome; T-Lymphocytes

Investigations were performed in 6 cases of epidermodysplasia verruciformis and 2 healthy family members. Nonspecific cell-mediated immunity (CMI) was studied by measuring response to phytohemagglutinin (PHA) and concanavalin A (Con A), percentrages of E- and EAC-rosette-forming lymphocytes, bacterial skin tests, and allergic reactions to dinitrochloro-benzene (DNCB). Impairment of CMI was manifested by reduction in the percentage of E rosettes, and lowered response to PHA, and- to a lesser degree- to Con A. The immune response to DNCB sensitization was invariably negative. Impairment of CMI was greater in cases of long duration and with extensive lesions. The cases of similar duration and extent of lesions, which never showed tendency to tumor formation, were not different in CMI in comparison with cases with numerous tumors. Only in cases with very advanced tumors CMI was impaired parallel to the gravity of the patient's general condition.

Topics: Adolescent; Adult; Child; Concanavalin A; Dinitrochlorobenzene; Female; Humans; Immunity, Cellular; Lectins; Lymphocyte Activation; Lymphocytes; Male; Precancerous Conditions; Skin Diseases; Skin Tests; Syndrome

Topics: Adult; Animals; Antilymphocyte Serum; Bone Marrow; Bone Marrow Cells; Cattle; Cell Differentiation; Cell Separation; Cells, Cultured; Concanavalin A; Epitopes; Erythrocytes; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; Infant; Lectins; Male; Mitomycins; Parathyroid Glands; Sheep; Spleen; Syndrome; T-Lymphocytes; Thymidine; Thymosin; Thymus Extracts; Thymus Gland; Tissue Extracts; Transfer Factor; Tritium

Immunological and pathological studies in a case of partial Di George syndrome revealed an absence of parathyroids, a major hypoplasia of thymus but a relatively moderate decrease in peripheral T-lymphocyte numbers and functions. After in vitro incubation with normal thymus extracts, a normal proportion of bone marrow cells was induced to differentiate into cells with characteristics of T lymphocytes, thus establishing the presence of T-cell precursors in the patient's bone marrow.

Topics: Antigen-Antibody Reactions; Antilymphocyte Serum; Bone Marrow; Bone Marrow Cells; Concanavalin A; Female; Humans; Immunologic Deficiency Syndromes; Infant; Lymph Nodes; Lymphocyte Activation; Parathyroid Glands; Spleen; Syndrome; T-Lymphocytes; Thymus Gland; Transfer Factor