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J P Dessaint

Publications and source records attributed to J P Dessaint.

At least 19 recordsLinked to original sources
PubMed1992

Immunologic aspects of schistosomiasis.

Immunity to schistosomes, helminth worms that infect 200 million people, is targeted to invading larvae (concomitant immunity). In vitro studies have revealed the role of T cells and of particular antibody isotypes in immune defense: IgE antibody cooperates with mononuclear phagocytes, eosinophils, and platelets to kill schistosome larvae. IgE antibody appears as an essential component of acquired resistance in rats. The role of IgE antibody has recently been confirmed by epidemiological studies demonstrating a positive correlation between the acquisition of resistance to reinfection by schistosomes and the level of IgE antibody to the parasite. A negative correlation found in these studies with the levels of IgM, IgG2, or IgG4 antibodies could be related to the development of a blocking antibody response. Antigens involved in protective immunity are expressed transiently at the surface of schistosomes. Sm28, a glutathione-S-transferase, induces significant protection against schistosome infection in rodents and nonhuman primates. In addition, this vaccine reduces the size of egg granulomas and egg output. Besides allowing the definition of a vaccine strategy against a major disease, studies on immunology of schistosomiasis have unraveled unsuspected antigenic mimicry between schistosomes and HIV regulatory proteins and have led to the demonstration that IgE antibody, a protective isotype against helminths, may also activate Fc epsilon-RII-bearing mononuclear phagocytes, eosinophils, and platelets in allergic disease.

Animals↗
PubMed1992

Vaccine strategies against schistosomiasis.

In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totally permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxicity (ADCC) involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tissue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets), interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the establishment of a future vaccine against Schistosoma mansoni.

Animals↗
PubMed1992

Vaccine strategies against schistosomiasis.

Schistosomiasis, the second major parasitic disease in the world after malaria affects at least 200 million people, 500 million being exposed to the risk of infection. It is widely agreed that a vaccine strategy which could lead to the induction of effector mechanisms reducing the level of reinfection and ideally parasite fecundity would deeply affect the incidence of pathological manifestations as well as the parasite transmission potentialities. Extensive studies performed in the rat model have allowed the identification of novel effector mechanisms involving IgE antibodies and various inflammatory cell populations (eosinophils, macrophages and platelets) whereas regulation of immune response by blocking antibodies has been evidenced. Recent epidemiological studies have now entirely confirmed in human populations the role of IgE antibodies in the acquisition of resistance and the association of IgG4 blocking antibodies with increased susceptibility. On the basis of these concepts, several schistosome target proteins have been identified and their encoding genes cloned. One of them, a schistosome glutathione S-transferase (Sm 28 GST) appears as a promising vaccine candidate. Immunization experiments have shown that two complementary goals can be achieved: (a) a partial but significant reduction of the worm population (up to 60% in rats); (b) a significant reduction of parasite fecundity (up to 70% in mice and 85% in cattle) and egg viability (up to 80%). At least two distinct immunological mechanisms account for these two effects. IgE antibodies appear as a major humoral component of acquired resistance whereas IgA antibodies appear as a major humoral factor affecting parasite fecundity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Improved permeabilization procedure for flow cytometric detection of internal antigens. Analysis of interleukin-2 production.

A cell membrane permeabilizing treatment is described which involves the use of lysolecithin at low concentration in acidic acetate buffer and paraformaldehyde fixation. It preserved well-separated scatter cytograms of small and large lymphocytes. The accuracy of the immunochemical detection of internal antigens by flow cytofluorography was demonstrated by the linear relationship between the percentage of fluorescent cells detected and the proportion of intracellular antigen-containing cells in mixtures with antigen-negative cell lines. Cell cycle analysis by dual nuclear staining with propidium iodide and FITC-conjugated Ki-67 antibody recognising in vitro stimulated human T lymphocytes verified that the proliferating lymphocytes retained their increased light scatter properties after permeabilization. Enumeration of interleukin-2 (IL-2) producing cells by their cytoplasmic immunofluorescence showed that enlarged lymphocytes were the main IL-2 producing cells. This improved permeabilization procedure, by gating small and enlarged lymphocytes separately, makes it possible to determine by two color fluorescence the immunophenotype of activated T cells committed to interleukin production.

Cell Cycle↗
PubMed1991

Neutrophil-endothelial cell interaction: evidence in vitro for a regulation by endothelial cells of neutrophil functions.

The purpose of this study was to investigate a possible relationship between human umbilical vein endothelial cells (EC) triggered by ionophore A23187 at different doses (0.5-2.5 microM) and polymorphonuclear neutrophils (PMN). EC supernatants were shown to contain neutrophil chemoattractant activity (NCA) and in parallel a factor inducing an inhibition of PMN chemiluminescence (PMN CL). Supernatants obtained from EC triggered by A23187 exhibited a high level of NCA (73 +/- 5 PMN.hpf-1 compared to 21 +/- 4 PMN.hpf-1 in untreated EC supernatants, p less than 0.01). This NCA was independent from arachidonic acid metabolites, since indomethacin and nordi-hydroguaiaretic acid failed to suppress the chemotactic activity. Using gel filtration chromatography (AcA 54) the NCA was recovered in a single peak of apparent molecular weight of 37,000 +/- 4,000 daltons. Checkerboard analysis indicated that NCA exhibited both chemotactic and chemokinetic activities. In addition, supernatants of A23187-stimulated EC, and at a lesser degree, supernatants of unstimulated EC, inhibited PMN CL induced by N-formyl-Methionyl-Leucyl-Phenylalanine (61% inhibition, p less than 0.05), and by A23187 itself (80% inhibition, p less than 0.01), but not that induced by phorbol-myristate-acetate. Indomethacin and protamine sulphate did not modulate this inhibitory activity. By contrast, EC-derived inhibitory activity was inhibited (50%) by an adenosine antagonist (8-phenyltheophylline), indicating a participation of adenosine in this inhibitory activity of PMN CL. These data suggest the possibility that activated endothelial cells could both enhance PMN migration and protect themselves against potential damaging effects of oxygen metabolites produced by PMN, particularly during transvascular migration.

Calcimycin↗
PubMed1990

Comparison of the effects of purified human alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor on NK cytotoxicity: only alpha 1-proteinase inhibitor inhibits natural killing.

While an inhibitory effect on natural killer (NK) cell activity was demonstrated with partially purified alpha 1 Achy, neither highly purified alpha 1 Achy from two healthy donors nor from one patient with giant-cell arteritis, which carries more highly branched glycans, inhibited the NK cytotoxicity. Our purification procedure, based on immunoaffinity chromatography and gel filtration, was not in question since the pure alpha 1-proteinase inhibitor (alpha 1PI) prepared in our laboratory by using a similar procedure continued to inhibit the NK cytotoxicity. If an inhibitory effect not related to antiprotease activity occurs with alpha 1PI, it is surprising that it is not shared by alpha 1 Achy which, like alpha 1PI, belongs to the serpin family and which possesses a strong structural homology with alpha 1PI. Our finding that alpha 1PI is able to affect human NK cytotoxicity while alpha 1 Achy (even with more highly branched glycans) is unable to suggests that events controlling NK activity may involve other enzymes than chymotrypsin-like enzymes.

Arteritis↗
PubMed1990

Isotypic profiles of antibody responses to Toxoplasma gondii infection in rats and mice: kinetic study and characterization of target antigens of immunoglobulin A antibodies.

The antibody responses to Toxoplasma gondii were investigated in rat and mouse experimental models. The immunoglobulin A (IgA) antibody response was of particular interest because acquisition of Toxoplasma gondii is usually by the oral route. The rat model was used because the natural resistance of rats to the parasite is similar to the natural resistance exhibited by adult humans. There was an early and simultaneous rise in IgA and IgM antibody responses. The IgA antibody response was maximal around day 40. IgA antibodies from Fischer rats were mainly directed against soluble and membrane antigens of 28.5, 29, 30, 35, and 38 kilodaltons (kDa). In mice, however, a major antigen of 29 kDa was recognized by IgA antibodies. Moreover, in orally infected rats, an intense IgE antibody response against the major surface antigen, P30, was observed. An IgA antibody response was also observed in rats and mice immunized with Toxoplasma excreted-secreted antigens, even without adjuvant. This response was mainly directed against 28.5- and 34-kDa antigens in rats. Serum IgA from infected rats tested against the excreted-secreted antigens bound to 28.5- 34-, and 39-kDa antigens, whereas sera from infected mice recognized only the 34-kDa antigen.

Animals↗
PubMed1989

IgE and inflammatory cells.

Extensive studies initiated in parasitic disease models have unequivocally established that IgE antibodies can directly interact with mononuclear phagocytes, eosinophils and platelets through specific surface receptors now identified as Fc epsilon RII. Genes coding for B cell and more recently eosinophil IgE receptors have been cloned. Studies on molecular structure indicate a close homology between Fc epsilon RII on inflammatory cells and on B cells but indications are emerging of some degree of heterogeneity among the second class of receptors for IgE. Recent studies performed in parallel on eosinophils indicate that their IgE receptors contain a sequence commonly involved in the primary structure of adhesion proteins. Interaction between antigen and cytophilically bound IgE antibodies results in the triggering of cell effector function and the release of a variety of pro-inflammatory or cytocidal mediators. Among others, one eosinophil granule protein (eosinophil peroxidase) is preferentially released by anaphylactic isotype-dependent stimuli. The main expression of IgE-dependent platelet activation appears related to the production of oxygen-derived free radicals (detected by chemoluminescence and electron magnetic resonance) together with their cytocidal properties. Taken together these findings confirm our current view that IgE receptors on inflammatory cells play a major role in the expression of cell effector function, both in defence mechanisms against several parasites and in allergic reactions.

Animals↗
PubMed1989

Schistosoma mansoni-specific rat T cell clones. II. Different effects of adult worm-specific T cell clones in immunocompetent and nude infected rats.

The in vivo functional activities of two highly proliferating helper rat T cell clones (E23 and G5) specific for the excretory-secretory antigens of Schistosoma mansoni adult worms were investigated. When injected into infected immunocompetent rats, both clones increased the antibody response against the 30-40-kDa schistosomulum surface antigens, but failed to induce an immune protection. In contrast, when the same clones were injected into infected nude rats, a high degree of protection was obtained. In this latter case the absence of detectable specific antibody response, whether of IgE or IgG isotype, suggested that parasites were destroyed by an antibody-independent mechanism, i.e. macrophages activation by lymphokines. Indeed supernatants obtained from T cell clones specifically restimulated with schistosome antigens expressed a macrophage activated activity similar to interferon-gamma. Following incubation with these supernatants or with the active fractions, macrophages exhibited a significant schistosomulicidal activity and both clones were shown to transfer an antigen-specific delayed-type hypersensitivity reaction to normal rats. Taken together these results demonstrate that, depending on the immune status of the host, antigen-specific T cell clones can function differently and consequently that one function associated with one type of lymphokine could be favored.

Animals↗
PubMed1989

IgE and inflammatory cells: the cellular networks in allergy.

The expression by macrophages, eosinophils, and platelets of IgE receptors (Fc epsilon RII) confers on these cells, present or recruited at the site of allergen challenge, a direct role in the development of adverse allergic reactions. The IgE-dependent activation of macrophages, eosinophils, and platelets is moreover inhibited by antiallergic drugs such as disodium cromoglycate or nedocromil. This network of IgE-dependent effector cells is controlled by immunoregulatory pathways which can be target of desensitization therapy. Contrary to their deleterious role in allergic disorders, IgE- and Fc epsilon RII-bearing cells play a decisive role in the immune defense against helminth parasites, therefore pointing to a dualistic function of IgE.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Concomitant augmentation of CD4+ CD45R+ suppressor/inducer subset and diminution of CD4+ CDw29+ helper/inducer subset during rush hyposensitization in hymenoptera venom allergy.

A longitudinal study of patients undergoing rush hyposensitization by honey-bee or yellow jacket venom revealed significant changes of the immunophenotypes until the optimal dose was reached, and a progressive reversion to pre-treatment values in the following months. The activation markers CD23 on B cells and CD25 (IL-2 receptor) on T and B lymphocytes decreased. Although there was little variation of the major CD4 and CD8 lymphocyte populations, CD45R+ cells increased whilst CDw29+ lymphocytes diminished. This inverse variation was associated with a peak of CD4+ CD45R+ cells with concomitant decrease in CD4+ CDw29+ cells showing an inverse effect of the treatment on the reciprocal subsets of CD4 lymphocytes. This indicates a shift in the suppressor/inducer to helper/inducer cell ratio early during rush hyposensitization which may also suggest reversion into a less mature stage of CD4+ cells, associated with the transition from a highly allergen-reactive state to progressive unresponsiveness.

Adolescent↗