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Biomedical subjects

G Chaouat

Publications and source records attributed to G Chaouat.

At least 163 records · Page 9Linked to original sources
PubMed1976

Influence of reticuloendothelial blockade on the induction of tolerance and immunity by polysaccharides.

The intensity of reticuloendothelial blockade by carrageenan, silica and ethyl stearate was measured and its effect studied on the susceptibility to tolerance induction by polysaccharide antigens in mice. The most intense RE depression reduced the tolerance threshold dose of levan only by 3-fold and that of dextran B512 not at all. The genetic resistance of BALB/c mice to tolerization with the alpha1-3 glucose epitope of dextran B1355 was not overcome by carrageenan blockade which did however, render them normally susceptible to tolerance induction by human gamma-globulin. PFC responses to immunization by the polysaccharides were diminished by blockade, relative to its intensity and to the antigen itself. These and other data suggest that severe RE blockade (a) can promote tolerance by suppressing the active role(s) of the macrophages in immune induction rather than by sustaining circulating antigen, and (b) depresses responses to thymus-independent antigens, probably by an immunosuppressive influence mediated by damaged macrophages.

Animals↗
PubMedDate not supplied

Multiple low-dose tolerance to human gamma globulin: respective roles of T-cell suppression and direct T-helper paralysis.

Spleen cells of mice rendered tolerant to human gamma globulin tolerogen by multiple low-dose injections were transferred with immune spleen cells into syngeneic irradiated recipients, then challenged with immunogen. The suppressive effect of the spleen from tolerant animals was abolished by anti-Lyt-2 + C' treatment, which enabled also purified T cells to deliver a certain amount of help to immune B cells. It is therefore suggested that, at least in CBA strain, part of the T-cell tolerance depends upon continuous suppressor T-cell action in this system. Nevertheless, part of the functional incapacity of the helper population is probably due to direct paralysis. Thus both suppression and clonal inactivation are involved in multiple low-dose tolerance.

Animals↗
PubMedDate not supplied

The in vivo antibody response to hen egg white lysozyme in H-2b-compatible responder and non-responder mice: is it regulated by its N-terminal peptide at the level of antigen-presenting cells?

We studied the in vivo antibody responses of three H-2b strains, BALB/b, C57BL/6 and BALB/B x C57BL/6 F1 to various lysozymes, REL and HEL, after priming with HEL, REL or the HEL N-terminal peptide. It was confirmed that C57BL/6 is a non-responder strain to HEL and that BALB/b is responder strain. The C57BL/6 non-responder trait was associated with HEL or peptide induction of suppressor cells, as shown by adoptive transfer experiments. We further demonstrated that the suppressor/non-responder trait is dominant in BALB/b x C57BL/6 F1 hybrids and that appropriately pulsed macrophages of BALB/b mice can bypass such suppression in these F1 mice. Possible mechanisms are discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Evaluation of the placental environment with a new in vitro model of histocultures of early and term placentae: determination of cytokine and chemokine expression profiles.

We aimed to set up and validate a new in vitro model of placental histocultures, for the evaluation of cytokine and chemokine profiles of the placental environment, over a long culture period. Micro-explant cultures from 6 early and 6 term placentae were set up on collagen sponge gel supports at a liquid/air interface. At various times during culture, we analyzed tissue morphology and cell death by microscopy and quantified beta-hCG production and mRNA levels for beta-hCG and insulin-like 4 (INSL4). Levels of IL-6, LIF, TNF alpha, IL-10, IFN-gamma, IL-16 and RANTES in the medium were measured by ELISA on days 1, 4 and 7 of culture. SDF-1 mRNA expression was determined by real-time PCR at the same time points. Histocultures from early and term placentae remained viable until day 10. High levels of IL-6 and LIF production, low levels of TNF alpha, IL-10 and IFN-gamma production and significant SDF-1 expression were observed. These data indicate that placental histoculture is a suitable and reliable in vitro model for studying the placental environment.

Adult↗
PubMedDate not supplied

Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatments.

There have been important advances in basic science investigation of mechanisms underlying spontaneous miscarriages which lend support to empirical treatments such as intravenous immunoglobulin G and allogeneic leukocyte immunotherapy. The results from clinical trials of these and other proposed treatments have been problematic. There is only one published meta-analysis of sufficient power and appropriate stratification to qualify as Level 1 evidence, and that deals only with leukocyte immunotherapy. Here we critically review current trials and their flaws, update the meta-analysis, and comment on potential new approaches. Inadequate sample size, better definition of heterogeneity, and proper stratification to minimize the effects of heterogeneity remain as problems. Verification that the experimental or test treatment was active in producing the expected alteration in immunophysiology in the recipient is lacking in most trials; use of stored rather than fresh allogeneic leukocytes appears problematic. Hidden biases that affect trial significance emerge with critical analysis, and the focus on apparent 'high quality' of design in published reports may be misleading. We conclude that there seem to be enough patients to conduct clinical trials of sufficient size to achieve adequate power to test therapies showing promise in pilot studies, but at present, the only Level 1 evidence concerns leukocyte immunotherapy which appears to increase the chance of a live birth if given to appropriate patients.

Abortion, Habitual↗
PubMedDate not supplied

Cytokines and anorexia nervosa.

OBJECTIVE: Recent studies have indicated that the inflammatory cytokines could be implicated in anorexia nervosa and in its complications. To determinate the potential role of interleukins (IL-1, IL-2, IL-4, IL-6, IL-10), interferon (IFN gamma), tumor necrosis factor (TNF-alpha), and transforming growth factor (TGF-beta2) in anorexia nervosa, serum concentrations of these cytokines were measured in patients suffering from anorexia nervosa in comparison to healthy subjects. METHOD: Twenty-nine anorexic women according to DSM-IV criteria participated in the study. The control group consisted of 20 healthy women without eating disorders, mood disorders, and immunological disorders. RESULTS: We find that serum IL-2 and TGF-beta2 concentrations were both significantly decreased in anorexic patients, although the other cytokines did not differ significantly between the two groups. CONCLUSION: Our results show that in patients with anorexia nervosa, there are lower levels of specific cytokines (especially IL-2 and TGF-beta2). These levels may reflect the combination of impaired nutrition and weight loss, therefore, the dysregulation of these cytokines may contribute in anorexia's complications. Follow-up studies should examine the effects of parameters such as starvation, psychopathologic factors, and psychoneuroendocrinological perturbation which could affect interplay between cytokines, neuropeptides, and neurotransmitters.

Adolescent↗
PubMedDate not supplied

Systemic active suppression is not necessary for successful allopregnancy.

To investigate the role of systemic suppression during allopregnancy, CBA/J female mice were immunised against H-2d prior to mating. Cytotoxic T lymphocyte (CTL) activity was tested at days 14-16 of pregnancy. A reduction of CTL activity was observed only in multiparous animals. Although a nonspecific suppression was detected in isopregnancy, suppression was more marked in allopregnancy. Conversely, the CTL activity observed in the spleen during the first pregnancy (iso or allo) was always significant in mice presensitized with 2 or 3 alloimmunizations prior to pregnancy. Such animals have in vivo effector cells, since allografts of Sarcoma Sa1 were rejected in secondary fashion in alloimmunized mice, while the fetus remained unharmed. These observations demonstrate that allospecific anti-MHC CTLs are specifically impaired in multiple allopregnancy, but also tend to rule out theories postulating that systemic suppression of CTL generation and function is required for successful allopregnancy.

Animals↗
PubMedDate not supplied

Placental products induce suppressor cells of graft versus host reaction.

Cells from mice alloimmunized in the presence of placental extract were coinjected with cells from mice conventionally alloimmunized in the footpad of virgin female recipients. The contralateral footpad received a control twice the dose of cells from alloimmunized mice. Cells from the popliteal lymph nodes were harvested on day 3, and pulsed in vitro for measurement of proliferative capacity with 3H thymidine. The response of lymph nodes was compared (homo- vs contralateral). The cells from mice alloimmunized with placental extract in conjunction with alloantigens displayed a marked suppressive capacity of the local graft versus host (GVH) potential of cells from mice conventionally alloimmunized. It is suggested that this local GVH assay represents a quick, objective assay for suppressor-cell induction by placental products.

Animals↗
PubMedDate not supplied

Immunoactive products of human placenta (III): Characterization of an inhibitor affecting lymphocyte proliferation.

We have investigated the effects of supernatants from human placenta explant cultures on lymphokine dependent T cell proliferation using mainly the CTLL-2 reference murine cell line. A profound, dose dependent, inhibition of both IL-2 and IL-4-dependent cell proliferation was observed. In addition, supernatants from human placental cultures inhibited B cell proliferation, IL-5-driven proliferation of B13 cells, and IL-6-induced proliferation of 7TD.1. Conversely, the supernatants from human placental cultures enhance the growth of human embryonic fibroblasts. Characterization of the material by HPLC yielded a 68-70 kDa peak at pH 7.4, but the peak activity was at a smaller molecular weight (20-25 kDa) if pH 2.9 acetic acid, KC1 buffer was used. The same fractions were inhibitory for IL-2 and IL-4 driven proliferation of CTLL-2 cells. We conclude that the substances tested are acting as a general growth inhibitor for lymphocytes.

Animals↗
PubMedDate not supplied

Maternal T cells regulate placental size and fetal survival.

The placental immunotrophism hypothesis states that maternal T cells, through their lymphokines, exert a positive influence on placental growth, which can lead to improved chances of fetal survival. We report here that deleting maternal T cells by monoclonal antibody injection during midgestation is accompanied by increased fetal resorption and decreased placental weight and phagocytosis in two different strain combinations of mice. Conversely, mice with T-cell proliferative disease show increased placental weight and phagocytosis, which can be reversed following T-cell depletion during pregnancy. Furthermore, female mice that are prone to fetal resorption show improved fetal survival if injected with spleen cells from mice with T-cell proliferative disease. These results are in accord with predictions of the placental immunotrophism hypothesis and imply that maternal T cells can participate in the prevention of spontaneous fetal resorption.

Animals↗
PubMedDate not supplied

The possibility of antiidiotypic activity in multipareous mice.

CBA females pregnant of A/J males were tested for the presence in their sera of antiidiotypic antibodies, capable of combining with antipaternal Ig determinants. Radioimmunoassay tests have shown that in comparison to females pregnant of isogeneic males, allopregnant sera presented values indicating the presence of an antiidiotypic reaction in five out of seven trials. The possible role of antiidiotypic reactions in the control of maternofoetal relationship is discussed.

Animals↗
PubMedDate not supplied

[Genetic restrictions of the HGG high-zone tolerance specific suppressive factor: arguments against a direct macrophage involvement (author's transl)].

Human gamma-globulin (HGG) high-dose tolerance spleen cell factor is shown to be genetically restricted. Yet, macrophages are not required for its production; and BALB/c mice, whose macrophages are hyperactive, can be tolerized partially by H-2d compatible factor or factor produced by BALB/c mice previously rendered sensitive to tolerance induction by carrageenan pretreatment. Thus, direct, involvement of macrophages in genetic restrictions appears unlikely. Since iron powder treatment unveils an amplifier effect of the crude supernatant from tolerant cells, it is suggested that specific and non-specific amplification coexists with suppression at day 5 of HGG-tolerance induction. Thus, interaction between an IJ+ suppressor T cell and an IJ+ amplifier cell or helper cell (or its precursor) is suggested to account for the observed genetic restrictions.

Animals↗
PubMedDate not supplied

[Human gammaglobulin tolerance: shared idiotypy of T-cell suppressor factor and antibodies (author's transl)].

A factor from human gammaglobulin (HGG) high-zone-tolerant CBA splenic T cells has been produced in optimal conditions after a 16-h culture in CBA mice. A CBA anti-(CBA anti-HGG) serum, purified on HGG, and referred to as antiidiotypic serum, has been coupled to Sepharose-4B. The factor can be adsorbed by this antiidiotypic serum but to a smaller extent than by anti-Iak. The existence of shared idiotypic determinants by factor and antibodies is discussed.

Animals↗
PubMedDate not supplied

Immunoactive products of murine placenta. II.--Afferent suppression of maternal cell-mediated immunity by supernatants from short-term cultures of murine trophoblast-enriched cell suspensions.

Supernatants from short-term cultures of mid-term murine trophoblast cells were assayed for their in vitro regulatory potential. They markedly inhibited cell-mediated lympholysis and mixed lymphocyte reaction in a non-specific, non-restricted fashion. By contrast, the mitogenic response to optimal doses of ConA was unaffected, while the plaque-forming cell response to sheep red blood cells was either unmodified or slightly enhanced. These data suggest that placenta-derived cells secrete factors which selectively impair some cell-mediated immune responses. It is suggested that these factors play an important role in the lack of generation of cytolytic T lymphocytes towards paternal alloantigens expressed on the trophoblast during allopregnancy.

Animals↗
PubMedDate not supplied

[Are desquamated trophoblastic cells retrieved from the cervix suitable for a prenatal diagnosis?].

Prenatal diagnosis based on sampling of fetal tissues, amniotic fluid or chorionic villi is associated with the risk of miscarriage and fetal damage. These risks would be avoided if diagnosis could be performed in desquamated trophoblast cells recovered non-invasively from the maternal cervix. We report on our experience of fetal karyotyping on endocervical lavage using in situ hybridization (FISH) and DNA amplification (PCR) fetal sex was correctly predicted in 8/10 cases by FISH and in 6/10 by PCR. FISH appeared to be a reliable technique for karyotyping when trophoblast can be recovered from the maternal endocervix (8/10).

Female↗
PubMedDate not supplied

Mechanism of T-cell suppression in tolerance to HGG: arguments in favor of a T-cell-T-cell interaction.

The specific soluble factor from suppressor T cells of CBA mice rendered tolerant to human gammaglobulin was further investigated. Immunochemical analysis proved the low zone tolerance (LZT) factor to be similar as the one described in high zone (HZT), e. g. absorbed by anti-Iak or IGG but not anti-HGG or anti-IgG. Molecular weight was ascribed as 45--55,000 by Sephadex chromatography and "Amicon" ultrafiltration. The HZT factor acts only if administered early after challenge, and on T cell as judged by double transfer experiments, suggesting impairment of early T-cell function (helper?) by suppressor cells.

Animals↗
PubMedDate not supplied

[Enhancing antibodies and supressive cells in maternal anti-fetal immune reaction].

Some of the mechanisms of tolerance to the foetal allograft have been studied in vivo, both at cellular and humoral level. It has been shown that immunoglobulins, mostly IgG1, can be detected and eluted from the placenta of allogeneic and syngeneic pregnancies in a wide variety of combination (CBA, C57Ks A/Jax, Balb C, DBA2). These immunoglobulins, in the case of allogeneic pregnancy, bind to paternal thymocytes exclusively, demonstrating antibody activity toward paternal antigens. They promote (although partly "non-specifically") direct allogeneic mast cell degranulation. In vivo, eluates only from a C57Ks female X A/Jax male placenta exclusively induce a significant enhancement of SA1 (A/Jax, h-2a strain) tumor graft in C57Ks (H-2d) recipients. Intraperitoneal transfer of 1.0 to 1.7 X 10(7) spleen cells from C57Ks two weeks pregnant from A/Jax male does also promotes SA1 growth and survival. T and B enriched population, obtained by the nylon wool techniques, display similar activity. Further experiments are in progress to discard T cell contamination in the B enriched population and to study eventual macrophage involvement. Thus, two agents of the facilitation reaction--suppressor cells and enhancing antibodies--have been demonstrated in vivo during pregnacy, protecting the foetus against hazards of the rejection reaction, which is also demonstrates by other in vivo techniques in our laboratory.

Animals↗