Annales d'immunologie最新文献

The preceding paper described production and release of carcinoembryonic antigen (CEA) by in vitro culture of the human malignant melanotic melanoma (HMMC-ShAE+) cell line; the present paper reports on two findings related to CEA biofunction. 1) The function of cell membrane oligosaccharides on the antigen-antibody reaction, i.e. the binding of 125I-labelled monoclonal anti-HMMC-ShAE+ antibodies to enzymically modified HMMC-ShAE+ cells. In these experiments, two approaches were used: sequential treatment with exohydrolases and cultivation of the cells in media supplemented with nontoxic levels of tunicamycin and swainsonine. 2) The effect of grafting, into the hamster cheek pouch, of modified HMMC-ShAE+ cells on plasma CEA, plasma anti-CEA and antibody-dependent cell-mediated cytotoxicity. Commercially available 125I-labelled CEA and the "Abbott" enzyme-linked immunoassay were used to monitor plasma anti-CEA and CEA levels, respectively. 125I-deoxyuridine-labelled HMMC-ShAE+ were used to monitor plasma antibody-dependent cell-mediated cytotoxicity.

In the present work, it was demonstrated for the first time that the coelomic fluid of Lumbricus terrestris contained a substance recognized by human classical convertase. This substance permitted an immune, complement-dependent agglutination response of sheep erythrocytes carrying C3-convertase (EAC142). In addition, substances secreted by coelomic leukocytes possessed an inhibitory activity against human complement: the component C3 was cleaved into a C3b fragment. This result suggests the presence of a system the function of which is C3-convertase-like. We have thus shown that some complement functions, with their natural inhibitors, appear early in evolution. Certain of these functions and structures might be preserved throughout evolution.

We analysed the mechanisms of T-cell unresponsiveness to Mycobacterium leprae antigens and to unrelated antigens or T-cell mitogens in human leprosy and in an experimental model of murine infection by M. lepraemurium (MLM). In human leprosy, monoclonal antibodies OKT3, OKT4 and OKT8 were used to enumerate T-cell subpopulations within peripheral blood. Increased percentages of OKT8+ cytotoxic/suppressor cells were observed in untreated, non-reactional lepromatous patients. Conversely, lepromatous patients suffering from erythema nodosum leprosum, an Arthus-like phenomenon, exhibited a transient drop in the percentage of OKT8+ cells with a correlative increase in the proliferative response to T-cell mitogens. We studied the proliferative response to M. leprae of OKT4+ and OKT8+ cells isolated by a negative selection procedure using antibody-induced cytotoxicity plus complement. None of these subpopulations proliferated when incubated with M. leprae. In some patients, control treatment of mononuclear cells with complement alone induced the reappearance of a strong proliferative response to M. leprae, suggesting the existence of an active suppressor mechanism through soluble factors of an unknown nature. In MLM-induced murine leprosy, a progressive decrease was observed in the proliferative response to concanavalin A (ConA), and an early decrease in interleukin 2 activity in supernatants from ConA-stimulated spleen cells. Splenic T cells from MLM-infected mice transferred into naive recipients accelerated the local MLM growth in these recipients, suggesting that suppressor T cells may play a pathogenic role in the progression of MLM infection.

The activation of B cells to proliferate and secrete Ig is finely regulated by T cells and, at least under in vitro conditions, by T-cell products. In order to study the molecular mechanisms underlying the regulatory events, an adequate number of normal B cells at distinct stages of activation and lymphokine responsiveness must be obtained. This can be achieved by activation via the Ig receptor. Using this system, the following conclusions can be drawn. Induction of proliferation via the Ig receptor is a transient event. Proliferation can be maintained only if both the anti-Ig signal and B-cell growth factors are provided. Ig secretion can be induced by lymphokines in mu + delta + B cells stimulated by anti-mu or kappa, while mu + delta + B cells stimulated to proliferate by anti-delta need helper T cells for Ig secretion. In the nu/nu sheep red blood cell system, induction of hypomethylation of DNA is insufficient to lead to Ig secretion, but hypomethylation induced by azacytidine enhances an otherwise suboptimal induction of Ig secretion by lymphokines.

This work was designed to investigate the occurrence and evolution of autoantiidiotypic antibodies to double-stranded DNA in systemic lupus erythematosus (SLE). Serum samples from a patient with SLE who was submitted to repeated therapeutic plasmapheresis for 57 weeks were examined for the presence of autoantiidiotypic antibodies to DNA. Anti-DNA antibodies were affinity-purified from a serum sample obtained at the beginning of the observation period. Anti-anti-DNA activity, directed toward structures within the binding site of anti-DNA autoantibodies but not antibodies of another specificity, was detected in the serum of the patient. In addition, the decrease in the levels of anti-DNA antibodies took place concomitantly with a reciprocal increase in the autologous anti-idiotype. These results indicate that anti-DNA and anti-anti-DNA antibodies coexist in the serum of this patient, and suggest that antiidiotypic interactions may play a role in the modulation of idiotypic expression in SLE.

The human basophil degranulation test (HBDT) by anti-IgE antibodies was applied in 3 groups of subjects: 20 controls, 26 patients with helminthiasis and 28 allergic patients. Mean degranulation was higher in patients with helminthiasis than in the two other groups. A correlation was found between IgE serum level and HBDT results by anti-IgE (r = 0.373; p less than 0.02) with Spearman's rank correlation test. Therefore, degranulation with anti-IgE antibodies would appear to depend on the quantity of cell-bound IgE rather than on intrinsic basophil sensitivity.

The subcutaneous injection of polyacrylamide beads into mice induced an inflammation which allowed counting and characterization of inflammatory cells and substances contained within the granuloma. The cellular and protein content of the inflamed site was followed up for seven days. One day after injection of the beads, a large concentration of macrophages was found with a low content of polymorphonuclear leukocytes. No lymphocytes were observed. The increased protein concentration of the inflammatory exudate was accompanied by the appearance in the plasma of a protein with a pHi of 4.1 +/- 0.2. This protein, absent in normal plasma, was found 6 h after induction of the inflammatory reaction, with its concentration increasing up to the 4th day.

A quantitative assay for mouse monoclonal immunoglobulins (Ig) was made possible by a very simple and sensitive co-agglutination test. Staphylococci which were rich in protein A were used in the presence of sheep anti-mouse IgG (H + L) antibodies. The assay was conducted in a single step using micro-haemagglutination plates. Plates were scored after over-night incubation. This method could detect as little as 0.006 microgram of IgG/ml. One set of hybrids was screened both by this method and by an immunoenzymatic assay (ELISA): with one exception, all clones which were found to produce Ig by ELISA were also positive by co-agglutination. Moreover, the co-agglutination method detected 7 additional Ig-secreting cultures. The level of secretion of each positive hybridoma ranged from 0.2 to 2 micrograms/ml. Thus, when compared to ELISA, the co-agglutination test was not only just as sensitive, but was also much simpler and faster.