concanavalin-a and Sarcoidosis

Depressed ADCC activity was found in sarcoidosis patients in clinical Stage II when whole blood was used as the effector cell pool. Whole blood in Stage I patients as well as purified peripheral lymphocytes of sarcoidosis patients did not reveal a diminished cytotoxic activity. Stimulation experiments with PHA, Con A, and PPD in two different concentrations resulted in a normal PHA response, a significantly decreased Con A response (regardless of the clinical stage of the patients), and a significantly decreased PPD responsiveness of peripheral lymphocytes in Stage II patients, respectively. Regarding the distribution of peripheral B and T lymphocytes, only a significantly depressed T-cell number in Stage I sarcoidosis patients was observed. Peripheral cells forming EA and EAC rosettes and staining for membrane-bound immunoglobulins were within normal ranges. Serum antibody titers to different herpes viruses, including Epstein-Barr virus, were found not to be elevated. Twenty percent of sarcoidosis patients showed anti-immunoglobulins in their sera specific for the Fc and Fab fragment.

Topics: Adult; Antibodies, Viral; Antigen-Antibody Reactions; B-Lymphocytes; Concanavalin A; Cytotoxicity Tests, Immunologic; Herpesviridae; Herpesvirus 4, Human; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fc Fragments; Lectins; Lung Diseases; Lymphocyte Activation; Sarcoidosis; T-Lymphocytes; Tuberculin

Topics: Antigen-Antibody Reactions; B-Lymphocytes; Concanavalin A; Humans; Immunoglobulins; Lectins; Lymphocyte Activation; Sarcoidosis; T-Lymphocytes

The main immunocompetent cells in sarcoidal lesions are epithelioid cells and multi-nucleated giant cells (MGC), both of which are derived from monocyte-macrophage lineage cells. To understand further the relevance of monocytes in sarcoidosis, we examined in vitro MGC formation using monocytes from sarcoidosis patients, patients with other granulomatous diseases (OGD) and healthy control subjects. The supernatant of concanavalin A-stimulated peripheral blood mononuclear cells (conditioned medium) generated Langhans type-MGC and foreign body type-MGC from monocytes. Conditioned medium from any three groups had the same ability to form MGC from normal monocytes. On the other hand, MGC were more highly formed using monocytes from sarcoidosis patients than from other groups. When macrophages induced by treatment of monocytes with macrophage colony-stimulating factor (M-CSF) were used, the rate of MGC formation in sarcoidosis patients was about threefold or fourfold as much as that in OGD patients or healthy controls, respectively. Oxidized ATP inhibited MGC formation in all groups. The susceptibility of monocytes cultured in conditioned medium for 24 h to 2'- and 3'-o-(4-benzoyl-benzoyl)ATP-mediated cytolysis was significantly higher in sarcoidosis patients than other groups. These findings suggest that the ability of monocytes to form MGC through P2x7 receptors is enhanced in sarcoidosis patients.

Topics: Adenosine Triphosphate; Adult; Aged; Cell Fusion; Cells, Cultured; Concanavalin A; Culture Media, Conditioned; Female; Giant Cells; Humans; Macrophages; Male; Middle Aged; Monocytes; Receptors, Leukotriene B4; Receptors, Purinergic P2; Sarcoidosis

Lung macrophages may play an important role in the pathogenesis of pulmonary sarcoidosis. In this study, the ability of pulmonary macrophages and blood monocytes from sarcoidosis patients, normal controls and disease controls to provide the accessory signal necessary for the concanavalin A-induced activation of normal blood T cells was examined. Blood monocytes from all groups supplied a significantly greater accessory signal than lung macrophages. The accessory capacity of lavage macrophages from sarcoidosis patients varied over a wide range and correlations were sought between these values and other parameters of disease activity. Whilst there was no correlation with clinical parameters, accessory function of alveolar macrophages correlated significantly with the percentage of T helper cells in bronchoalveolar lavage (BAL) fluid (p less than 0.05) and, more closely, with the T helper:T suppressor ratio in BAL fluid (p less than 0.01). This interrelationship between macrophage activity and the T cell infiltrate favours the probability that both cell types participate in the sarcoid disease process and raises the possibility that T cells of both helper and suppressor phenotypes contribute to the pathogenesis.

Topics: Adult; Aged; Antigen-Presenting Cells; Bronchoalveolar Lavage Fluid; Concanavalin A; Female; Humans; Lung Diseases; Lymphocyte Activation; Macrophages; Male; Middle Aged; Monocytes; Pulmonary Alveoli; Pulmonary Fibrosis; Sarcoidosis; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

BAL and blood mononuclear cells and their reactivity to Kveim antigen, tuberculin and concanavalin A (Con A) were studied in nine patients with different clinical stages of sarcoidosis. After separation by plastic adherence, non-adherent cells (mainly lymphocytes) were admixed with 10% autologous adherent cells (monocytes/macrophages). After 3 and 6 days' culture with Kveim antigen (1, 10, 100 micrograms/ml), PPD tuberculin (2.5 micrograms/ml) and Con A (10, 20, 40 micrograms/ml) stimulation was measured as incorporation of 14C-thymidine into DNA. Except for occasional reactions the study did not show any unitary significant increase in lymphocyte response to the different concentrations of Kveim antigen in either BAL or blood. For Con A there was a weaker response by BAL-mononuclear cells with no difference between 3 and 6 days, compared with blood where there was an early peak. The lymphocyte reaction to PPD was weak with no difference between blood and BAL.

Topics: Adult; Bronchoalveolar Lavage Fluid; Concanavalin A; Female; Humans; Kveim Test; Leukocyte Count; Lung Diseases; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Sarcoidosis; Skin Tests; Stimulation, Chemical; Tuberculin

Granuloma formation in the lung of patients with sarcoidosis is preceded by the accumulation of large numbers of activated T-lymphocytes, which results, at least in part, from the proliferation of T-lymphocytes within the lung. To determine whether the increased proliferation of lung T-lymphocytes in sarcoidosis results from a failure of mechanisms responsible for limiting their proliferation, we have compared the ability of purified T-lymphocytes present in bronchoalveolar lavage fluid and peripheral blood from normal subjects and patients with sarcoidosis to respond to proliferative signals. The mitogen-induced proliferative response of lavage T-lymphocytes from normal subjects and patients with sarcoidosis was similar, but the response of lavage T-lymphocytes was much less than that observed using normal or sarcoid blood T-lymphocytes. The reduced proliferative response of sarcoid lavage T-lymphocytes could not be overcome by addition of accessory cells or exogenous interleukin-2, and it did not result from the presence of suppressor cells. Furthermore, sarcoid lavage lymphocytes are capable of being activated by "mitogenic" signals, as indicated by the ability of phytohemagglutinin to induce expression of the 4F2 surface antigen and stimulate interleukin-2 production. However, the expression of interleukin-2 receptors was reduced on stimulated sarcoid lavage T-lymphocytes compared with that observed on normal blood T-lymphocytes, which may account in part for their reduced proliferative capacity. Because mechanisms that render lavage T-lymphocytes from normal subjects refractory to proliferative signals appear to operate in sarcoidosis as well, these findings suggest that a defect in the inhibition of T-lymphocyte proliferation is unlikely to be an important cause of lymphocyte accumulation in this disorder.

Topics: Adult; Bronchoalveolar Lavage Fluid; Cell Division; Concanavalin A; Female; Humans; Interleukin-2; Lung Diseases; Major Histocompatibility Complex; Male; Phytohemagglutinins; Receptors, Antigen; Sarcoidosis; T-Lymphocytes

Topics: Animals; Cell Movement; Cell Separation; Cells, Cultured; Concanavalin A; Histamine; Humans; Lung; Lung Diseases; Lymphokines; Monocytes; Rats; Sarcoidosis; T-Lymphocytes, Helper-Inducer

Topics: Alveolitis, Extrinsic Allergic; Body Fluids; Bronchi; Concanavalin A; Cytotoxicity, Immunologic; Humans; Lymphocyte Activation; Pulmonary Alveoli; Pulmonary Fibrosis; Sarcoidosis; Therapeutic Irrigation

We have shown that peripheral blood monocytes from patients with sarcoidosis release reduced amounts of interleukin-1 (IL-1) when compared with normals. In part, this defect explains the relative in vitro unresponsiveness of T lymphocytes from patients with sarcoidosis as measured by mitogen- or antigen-induced lymphocyte transformation. The addition of supernatants containing pre-formed IL-1 partially restored this defect. This enhancement was found to be additive to the previously described effect of indomethacin, an inhibitor of prostaglandin synthesis. Thus, it would appear that the activated peripheral blood monocytes found in sarcoidosis not only cause reduced lymphocyte proliferation by acting as suppressor cells but are also unable to act as accessory cells in producing IL-1.

Topics: Adult; Aged; Concanavalin A; Dinoprostone; Female; Humans; Indomethacin; Interleukin-1; Lipopolysaccharides; Lung Diseases; Lymphocyte Activation; Male; Middle Aged; Monocytes; Prostaglandins E; Sarcoidosis; T-Lymphocytes

Increased suppressor T gamma lymphocytes have been described in sarcoidosis. We have shown that a proportion of these cells are esterase-positive, phagocytic, adherent to plastic and stain with an anti-monocyte serum. Removal of these cells or the addition of indomethacin increases the lymphocyte transformation to Con A. Transformation was still reduced in spite of preincubation with plastic and the addition of indomethacin suggesting that a further abnormality exists. Thus, within the increased number of T gamma cells there exists a population of activated monocytes which rosette with sheep red blood cells and could therefore be mistaken for T cells.

Topics: Adult; Aged; Cells, Cultured; Concanavalin A; Female; Humans; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Monocytes; Plastics; Rosette Formation; Sarcoidosis; T-Lymphocytes

Topics: Concanavalin A; Humans; Immunoglobulins; Sarcoidosis; T-Lymphocytes

Some in vitro functions of purified T and B cells from PPD- and Candida albicans-negative sarcoidosis patients were analyzed. It appears that in those patients there is: 1) A decrease in the absolute number of T lymphocytes and an increase in the number of B cells; 2) a rather normal response of T lymphocytes to PHA and Con A; 3) a rather normal capacity of T and B cells to produce MIF in vitro; and 4) an ability of T cells from sarcoid patients (but not B cells) to produce LMF. These results suggest that the frequent deficit in cell-mediated immunity observed in sarcoidosis seems to correlate with a quantitative deficit in T cells. The cause of this T-cell deficit is unknown.

Topics: Adolescent; Adult; B-Lymphocytes; Candida albicans; Concanavalin A; Humans; Immunity, Cellular; Lectins; Lung Diseases; Lymphocyte Activation; Lymphokines; Macrophage Migration-Inhibitory Factors; Middle Aged; Sarcoidosis; T-Lymphocytes; Tuberculin Test

Peripheral blood lymphocytes of nine patients with pulmonary sarcoidosis were collected before and after a standardized bicycle ergometer test. The lymphocytes were characterized by various cell surface markers as T or B lymphocytes, and functionally by mitogen- or antigen-induced DNA synthesis and by antibody dependent cell-mediated cytotoxicity. Physical work resulted in an increase of circulating lymphocytes. Proportionately more B lymphocytes were mobilized. The DNA synthesis of lymphocytes in response to mitogens and antigen was reduced, whereas the cytotoxicity was augmented. Compared with normals the mobilization of lymphocytes was less, and a deficiency of both T and B lymphocytes was revealed. The functional impairment of lymphocytes in the patient group persisted.

Topics: Adult; B-Lymphocytes; Concanavalin A; Cytotoxicity Tests, Immunologic; DNA; Humans; Lectins; Lung Diseases; Lymphocyte Activation; Male; Physical Exertion; Sarcoidosis; T-Lymphocytes

Topics: B-Lymphocytes; Cell Adhesion; Cell Separation; Concanavalin A; DNA; Humans; Immunity, Cellular; In Vitro Techniques; Lymphocyte Activation; Lymphocytes; Mitomycins; Sarcoidosis; T-Lymphocytes; Thymidine; Tuberculin

Topics: Animals; Antilymphocyte Serum; Azathioprine; B-Lymphocytes; Bacterial Infections; Concanavalin A; Dermatitis, Atopic; Graft Rejection; Hodgkin Disease; Humans; Immunosuppressive Agents; Kidney Transplantation; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Prednisone; Rabbits; Renal Dialysis; Sarcoidosis; T-Lymphocytes; Transplantation, Homologous

Topics: Candidiasis, Cutaneous; Cell Migration Inhibition; Concanavalin A; Erythema; Humans; Hypersensitivity, Delayed; Injections, Intradermal; Lectins; Lymphocytes; Macrophages; Sarcoidosis; Skin; Skin Diseases; Skin Tests

Topics: Acetylcholine; Adult; Brain; Brain Chemistry; Breast Neoplasms; Bronchial Neoplasms; Carcinoma; Cell Migration Inhibition; Concanavalin A; Epinephrine; Epitopes; Female; Histamine; Humans; Laryngeal Neoplasms; Lymphocytes; Macrophages; Male; Middle Aged; Myasthenia Gravis; Neoplasm Proteins; Neoplasms; Nerve Tissue Proteins; Norepinephrine; Sarcoidosis; Serotonin; Stomach Neoplasms; Succinylcholine; Tryptamines