concanavalin-a and Alveolitis--Extrinsic-Allergic

We previously reported that Trichosporon cutaneum was the major causative antigen of summer-type hypersensitivity pneumonitis (HP) in Japan. In summer-type HP patients, we noticed that the proliferative responses of bronchoalveolar lavage (BAL) lymphocytes to phytohemagglutinin (PHA) and concanavalin A were significantly lower than those of the peripheral blood lymphocytes of the same patients. It was shown in this study that the low response of BAL lymphocytes was due to an intrinsic lowering of the responsiveness of the T cells. Results of the mixed culture experiments, in which the responses to mitogens of BAL and peripheral blood T cells mixed with either alveolar macrophages or blood monocytes were compared, indicated that the decreased proliferative response was due neither to the suppressive effect nor to defects in accessory function of the alveolar macrophages. BAL T cells did not act as suppressor cells when they were added to the culture of peripheral T cells. The decreased proliferative response was not due to the dominance of CD8+ T cells frequently seen in BAL cells of HP patients, because both CD4+ and CD8+ T cells separated from BAL cells of HP patients showed lower responsiveness than those of peripheral blood T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Alveolitis, Extrinsic Allergic; Antigens, CD; Bronchoalveolar Lavage Fluid; CD18 Antigens; Cells, Cultured; Concanavalin A; Female; Gene Expression; Humans; Interleukin-2; Lymphocyte Activation; Macrophages; Male; Middle Aged; Phytohemagglutinins; Receptors, Leukocyte-Adhesion; RNA, Messenger; T-Lymphocytes; T-Lymphocytes, Regulatory; Trichosporon

T-cell suppression induced by concanavalin-A (Con-A) and the prostaglandin suppressor system (PSS) were studied in 14 patients with pigeon breeder's disease (PBD), 12 and 10 asymptomatic breeders, and 8 controls. Our results showed that PBD patients display a significant decrease in T-cell-induced suppression (29.6 +/- 15.3% vs. 61.2 +/- 9.3% in controls p less than 0.05); whereas asymptomatic breeders respond heterogeneously: 5 showed decreased suppression and 7 were within the normal range obtained in controls. In contrast, the patients presented a higher PSS index compared with the other 2 groups, suggesting an inverse relationship between the 2 systems. These findings indicate that there are relevant differences between PBD patients, asymptomatic breeders, and normal subjects in some immune interactions, which may at least partially explain the characteristic cellular and humoral hyperreactivity observed in patients with this disease.

Topics: Adult; Alveolitis, Extrinsic Allergic; Animals; Bird Fancier's Lung; Chronic Disease; Columbidae; Concanavalin A; Female; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Prostaglandins; T-Lymphocytes, Regulatory

The effect(s) of affinity-purified antibodies to pigeon serum immunoglobulins on normal T cell responses in vitro was measured. Our results show that the antibodies partially inhibited the concanavalin-A-induced proliferation of normal lymphocytes (32% at 10 micrograms/ml concentration; p less than 0.001), whilst they had no significant effects at equivalent doses on the phytohemagglutinin-induced response. A study of the kinetics of this inhibition revealed that the antibodies exerted their effect(s) within the first 24 h of culture (p less than 0.001); this is probably due to their interference in early events intimately involved in the de novo synthesis and expression of activation antigens such as HLA-DR and Tac: antibody-treated cultures expressed 51.6 and 41.4% less HLA-DR and Tac, respectively. Two-colour immunofluorescence analysis showed that the specific antibodies bind to a subset of CD8+ cells only.

Topics: Alveolitis, Extrinsic Allergic; Antibodies; Antigens, Differentiation, T-Lymphocyte; Binding Sites, Antibody; Binding, Competitive; Bird Fancier's Lung; Concanavalin A; Epitopes; Humans; Kinetics; Lymphocyte Activation; T-Lymphocytes

The importance of antibody and sensitized cells in hypersensitivity pneumonitis (HP) is unknown. In an attempt to create a model suitable for investigation of the mechanisms of HP, we transferred cells and serum from sensitized (Micropolyspora faeni in Freund's adjuvant) strain 2 guinea pigs to naive animals. Cells (peritoneal exudate, lymph node, or spleen) were cultured for 72 hours with either concanavalin A (Con A, 1 microgram/ml) or a soluble extract of M. faeni (10 micrograms/ml). We then injected the cells intravenously (IV) into naive guinea pigs, skin tested with purified protein derivative (PPD), challenged the animals intratracheally (IT) with M. faeni 48 hours after the cell transfer, and killed them 4 days (IT) with M. faeni 48 hours after the cell transfer, and killed them 4 days after IT challenge. We also transferred noncultured cells and antibody-containing serum from sensitized animals. Randomly selected microscopic fields of the lung (150 per animal) were judged to be normal or abnormal. All guinea pigs were maintained in high-efficiency particulate accumulator-filtered air. Compared with control animals that received media IV, there was a substantial increase (P less than 0.01) in the extent of pulmonary abnormalities in the animals receiving lymph node cells or spleen cells cultured with M. faeni, and peritoneal exudate cells cultured with Con A. Findings in recipients of peritoneal exudate cells cultured with M. faeni, or lymph node cells or spleen cells cultured with Con A did not differ from those in the control group. In contrast to cultured cells, noncultured cells and antibody-containing serum did not transfer susceptibility. PPD skin reactivity was present only in recipients of noncultured cells and not in recipients of serum or cultured cells. We conclude that experimental HP can be transferred with cultured cells from sensitized animals and that HP appears to be a cell-mediated process.

Topics: Alveolitis, Extrinsic Allergic; Animals; Antigens, Bacterial; Cells, Cultured; Concanavalin A; Guinea Pigs; Immunization, Passive; Lung; Lymph Nodes; Micromonosporaceae; Skin Tests

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

We have previously shown that inhaled Con A has a powerful enhancing effect on the formation of immune complexes between an inhaled antigen and circulating antibody. Immunohistochemical staining has demonstrated such complexes, together with host complement, in close association with foci of necrotizing destruction of the pulmonary parenchyma. We have postulated that Con A promotes immune complex formation indirectly through polyclonal activation of lymphocytes in the lung. In this paper we test this hypothesis in animals rendered unresponsive to Con A stimulation in vivo by i.v. administration of cholera toxin (CT). Such treatment raised the levels of cAMP in peripheral blood lymphocytes and inhibited their proliferative response to Con A in vitro. CT administration further blocked the local inflammatory response to intradermal injections of Con A, as well as the cell-mediated immune response to intradermal injections of BSA. Although CT failed to block the immune complex-mediated Arthus vasculitis in the skin, it did block production of immune complex pulmonary injury by antigen/mitogen aerosols, as did decomplementation with purified cobra venom factor. These findings support the hypothesis that polyclonal activation of pulmonary lymphocytes promotes immune complex-type alveolitis, possibly by facilitating interactions between humoral antibody and intra-alveolar antigen.

Topics: Aerosols; Alveolitis, Extrinsic Allergic; Animals; Antigen-Antibody Complex; Arthus Reaction; Cholera Toxin; Complement System Proteins; Concanavalin A; Cyclic AMP; Elapid Venoms; Immune Tolerance; Inflammation; Lung; Lymphocytes; Male; Rabbits; Serum Albumin, Bovine

An animal model of environmental lung disease is described in which phytomitogen, antigen, or both, are administered in aerosol form to previously immunized or immunologically naive rabbits. Inhalation of concanavalin A alone induced an interstitial pneumonitis in nonimmunized rabbits. Inhalation of concanavalin A alone induced an interstitial pneumonitis in nonimmunized rabbits. Inhalation of bovine serum albumin (BSA) alone typically produced only focal eosinophilic granulomas in BSA-immunized animals, and no injury whatever in nonimmune animals. However, simultaneous administration of BSA-concanavalin A aerosol mixtures to BSA-immunized rabbits induced a severe interstitial pneumonitis and granulomatous vasculitis, together with areas of frank parenchymal necrosis. When repeated on a chronic basis over a 4- or 8-week interval, challenge with BSA-concanavalin A aerosols resulted in both acute necrotic lesions as well as areas of frank interstitial fibrosis. Necrotic foci in acutely injured lungs were associated with interstitial deposits of BSA, rabbit anti-BSA antibody, and complement. Electron microscopy revealed numerous neutrophils within the pulmonary interstitial spaces of these animals, often in association with collagen and elastin fibers. The pattern of injury in immune rabbits induced by antigen-concanavalin A aerosols, in its nonnecrotizing form, is consistent with that of an extrinsic allergic alveolitis. However, the severe, necrotizing form of acute injury closely resembles changes seen in Wegener's granulomatosis. Possible mechanisms of injury produced by antigen and phytomitogen inhalation are discussed.

Topics: Aerosols; Alveolitis, Extrinsic Allergic; Animals; Concanavalin A; Drug Interactions; Lung; Male; Pulmonary Fibrosis; Rabbits; Serum Albumin, Bovine