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G Chaouat

Publications and source records attributed to G Chaouat.

At least 91 records · Page 5Linked to original sources
PubMed1993

Suppression of local and systemic GVHR by supernatants from human choriocarcinoma cell lines.

Graft versus host reaction (GVHR) and host versus graft reactivity during pregnancy share at least some cellular pathways. Immunosuppression mediated by placental suppressor factors may actively contribute to the survival of the conceptus in the immunocompetent mother. We have previously reported that supernatants from human choriocarcinoma cell lines inhibit mitogen-activated and antigen-activated proliferation of lymphoid cells. From this perspective, we investigated the capacity of supernatants from human choriocarcinoma cell lines (HCS) to suppress in vivo graft versus host reactions in mice. HCS was tested for its ability to block both local as well as systemic GVHR induced by the injection of parental cells into F1 mice. HCS mediates profound suppression of acute and chronic GVHR. These results confirm that human choriocarcinoma cell lines secrete a potent immunosuppressive factor(s) which can efficiently modulate immune responses in vivo.

Animals↗
PubMed1993

Effect of prostaglandin synthesis inhibitors on spontaneous and endotoxin-induced abortion in mice.

The putative role of prostaglandin E2 (PGE2) in suppressing rejection of the 'fetal allograft' (resorption) in C3H/HeJ and CBA/J allopregnant mice was tested by administration of the prostaglandin synthesis inhibitors indomethacin (INDO) and acetylsalicylic acid (ASA). When the resorption rate was low, INDO fed at a dose of 15 micrograms/ml in drinking water after implantation had a slight augmenting effect when the endogenous resorption rate was < 30%, but had no effect when the endogenous rate was higher or when bacterial lipopolysaccharide (LPS) was given. ASA fed at 50 micrograms/ml had no augmenting effect and did not increase sensitivity to the abortogen LPS in either CBA/J (LPS sensitive) or C3H/HeJ (LPS resistant) mice. Both INDO and ASA fed to CBA/J mice significantly reduced endogenous PGE2 extractable from the uteri of hormonally pseudopregnant mice after deciduoma induction. Feeding INDO at doses up to 30 micrograms/ml from day 2.5 of pregnancy impaired but failed to completely block implantation in CBA/J mice, and with daily administration, some of the mice became sick: all of the implants in sick mice resorbed. INDO at doses of 150-200 micrograms per day known to inhibit implantation in vivo by sufficiently blocking PGE2 synthesis, was injected on one or more days beginning after the time of implantation. This failed to cause abortion in CBA/J mice and although some mice became ill, provided this happened after day 8.5 of pregnancy when sensitivity to the abortogenic effects of injected LPS decreased substantially in these mice, all implants in the sick mice were 'healthy' (i.e. non-resorbing). We were unable to increase the rate of resorption in syngeneically pregnant CD1 mice above 13% with 15 ml INDO in drinking water. Our data do not support the view that PGE2 represents an important intrauterine suppressor molecular blocking the processes mediating embryo death at the time of abortion. Spontaneous abortion in DBA/2-mated CBA/J mice appears to be determined by the level of bacterial LPS (endotoxin) and treatment with antibiotics or intralipid (which enhances endotoxin clearance), reduces the abortion rate. A sufficient dose of INDO may cause abortion, but the data taken together suggest this may be due to effects on the gut whereby permeability to bacterial LPS is increased.

Abortion, Spontaneous↗
PubMed1993

Recombinant ovine trophoblastin (roTP) inhibits ovine, murine and human lymphocyte proliferation.

Ovine trophoblastic protein (oTP) is a 20-kDa embryonic secretory product constitutively secreted by ovine conceptus trophoblast from days 12-22 of pregnancy. Amino acid sequencing as well as molecular cloning revealed it to bear structural analogies with interferons of the class 2 alpha subfamily, defining the tau interferon group. It is endowed with classical interferon-like biological activities. Recombinant ovine trophoblastin (roTP), produced by genetic engineering, was purified by anion exchange HPLC to a high degree of homogeneity (98%). It behaved in immunodetection and antiviral activity assays like the natural form. We show here that when assayed on PHA-driven murine, human, and ovine (sheep) lymphocyte proliferation, roTP is immunosuppressive. It also inhibits unidirectional and bidirectional murine and human mixed lymphocyte reactions (MLRs). Since natural oTP possesses (at least) 5 isoforms, we also assayed these for immunosuppressive activities. All of them inhibited PHA-driven human and ovine lymphoblastogenesis. Finally, CD4+ and CD8+ ovine T cell selection was performed by panning. In contrast with earlier observations assaying roTP activity on human lymphocytes, both ovine CD4 and CD8 T cell subsets were sensitive to roTP in a PHA-driven proliferation assay. It is therefore suggested that trophoblast interferons might have a strategic function in preventing early embryonic demise by immunologic rejection, at least in ovine species.

Animals↗
PubMed1993

Stress-triggered abortion in mice prevented by alloimmunization.

PROBLEM: To determine if immunotherapy can prevent abortion triggered by mechanisms that in humans may be treatable by psychotherapy. METHOD: The effects of alloimmunization against paternal strain antigens were tested in pregnant mice subjected to stress. RESULTS: Restraint stress boosted the resorption rate assessed on day 13.5 of pregnancy in DBA/2-mated C3H/HeJ mice with an optimal effect on day 4.5 of pregnancy, and premating alloimmunization greatly reduced the effect. By contrast, CBA/J and A/J mice proved resistant to abortion boosting by restraint stress. A/J mice mated to DBA/2 or C3H/HeJ males showed reduced fertility, perhaps due to failure of pregnancy immediately after the stress, but this was not corrected by alloimmunization with either DBA/2 [class I + class II major histocompatibility complex (MHC) immunogen] or C3H/HeJ (class I MHC immunogen) splenocytes. There was a reduction in the endogenous resorption rate, however, and implantation number was slightly increased by preimmunization using DBA/2 cells. The abortion rate could be boosted, however, by ultrasonic noise stress of high abortion rate CBA/J, and preimmunization using BALB/c (H-2d) splenocytes protected. A similar boosting of loss in low abortion rate BALB/k mice was ameliorated (albeit not completely) by preimmunization with allogenic paternal but not syngeneic splenocytes. CONCLUSIONS: Immunotherapy may protect against a variety of potential triggers of spontaneous abortion, including those that may be amenable to psychological remedies, and possible mechanisms are discussed.

Abortion, Spontaneous↗
PubMed1992

The proportion of symmetric and asymmetric IgG antibody molecules synthesized by a cellular clone (hybridoma) can be regulated by placental culture supernatants.

The purpose of the present work was to establish whether the placenta is producing factors favoring an increased synthesis of asymmetric IgG antibodies which are known to assume a protective effect upon paternal antigens to which they largely are specific. In this way they can contribute to fetal survival in the maternal uterine environment. The hybridoma cell lines OKT8 (anti-CD8) and 112B4 (anti-DNP) were used in this respect since they synthesized both symmetric and asymmetric molecules of the IgG2a and IgG1 subclasses, respectively, murine isotypes in which anti-paternal antibodies have been detected. The cells were cultured in RPMI 1640 medium supplemented with 10% BCS and different amounts (5, 10, and 20%) of human placental supernatant. After incubation for 3 days at 37 degrees C in a humid chamber containing 5% CO2 the cells were centrifuged and the antibodies were obtained from the culture medium by a purification procedure involving precipitation at 50% ammonium sulfate saturation followed by DEAE-cellulose chromatography. Symmetric and asymmetric antibodies were separated by Con A-Sepharose affinity chromatography, the latter lectin retaining selectively only asymmetric IgG molecules. Both OKT8 and 112B4 hybridomas presenting a stable background synthesis of 15-17% of asymmetric antibodies have shown an increased level reaching 27-28% of these molecules in the presence of 5-10% placental supernatant added to the RPMI 1640 culture medium. These results clearly show that placental factors can up-regulate efficiently the synthesis of asymmetric IgG molecules of different isotypes secreted by plasma cells.

Animals↗
PubMed1992

Human trophoblast cells express CD4 and are permissive for productive infection with HIV-1.

The European collaborative study of HIV-infected pregnant women in Europe now indicates a 13% risk of fetal HIV infection (originally thought to be about 30%, and possibly higher in some countries). Several reports suggest trans-placental passage. However, the detailed mechanisms associated with such vertical transmission have not yet been clarified. We have examined the possibility that HIV enters placental tissue from maternal blood via binding to CD4 and Fc receptors (FcR) at the trophoblast level, allowing intraplacental infection. Here we report the detection of several FcR with distinct localization in the placental villus as well as CD4 surface expression on human trophoblast cells. In addition, we show that trophoblastic cells interact specifically with the gp120/gp160 viral envelope protein. By their tissue localization, these receptors could be responsible for the entry of HIV into the fetal placental cells. Furthermore, purified placental cells can be directly infected by HIV in vitro, and the infection is inhibited by soluble CD4. This suggests a crucial role of the CD4 receptor but an additional way of entry cannot be excluded. Such an in vitro model may be suitable for further studies concerning placental HIV transmission and its prevention.

CD4 Antigens↗
PubMed1991

In vitro and in vivo immunosuppressive effects of supernatants from human choriocarcinoma cell lines.

Local immunosuppression mediated by placental suppressor factors may contribute to the absence of consistently demonstrable cellular immunity against the fetus. In this context, we have investigated the immunosuppressive capabilities of supernatants from human trophoblastic choriocarcinoma cell lines (HCS) by testing the effects of HCS on immune responses in vitro and in vivo in the human and murine systems. HCS suppresses mitogen-induced proliferation and mixed lymphocyte reactions in humans and in mice, as well as antigen-induced T cell proliferation in mice. HCS also suppresses the in vivo response of mice to allogeneic cells. Furthermore, HCS when injected intraperitoneally causes the induction of suppressor cells in mice which in turn prevent the mounting of an allogeneic response in other strains of mice. These results indicate that human choriocarcinoma cell lines secrete a suppressor factor(s) which induces suppression in vitro as well as in vivo through the generation of suppressor cells.

Choriocarcinoma↗
PubMed1991

Immunoregulatory effects of ovine trophoblastin protein (oTP): all five isoforms suppress PHA-induced lymphocyte proliferation.

The immunosuppressive properties of ovine trophoblastin protein (oTP) isoforms purified to homogeneity by DEAE HPLC have been studied within and across species barriers by in vitro assays. It has been demonstrated that not only the classical oTP 1, but in fact all 5 isoforms, are immunosuppressive in a PHA-induced proliferation assay, whilst being ineffective on IL-2 dependent CTL-L2 cell replication. The significance of these findings is discussed.

Animals↗
PubMed1991

Immunoactive products of human placenta. IV. Immunoregulatory factors obtained from cultures of human placenta inhibit in vivo local and systemic allogeneic and graft versus-host reactions in mice.

We have shown in previous reports that human placental supernatants (HPS) display a variety of immunoregulatory properties in vitro. Here we report that these supernatants are able to suppress the ability of murine splenocytes to evoke an allogeneic reaction in the popliteal lymph node (PLN) assay, as well as their capacity to induce both local (popliteal lymph node swelling) as well as systemic chronic or lethal graft-versus-host reactions. Those results are discussed in the light of the potential use of HPS in the control of transplantation immune reactions as well as in the regulation of xenogeneic pregnancies, as the murine system that was used proved that the material exerted an effect across a species barrier.

Animals↗
PubMed1991

Hormonal and local factors control the immunohistochemical distribution of immunocytes in the rat uterus before conceptus implantation: effects of ovariectomy, fallopian tube section, and injection.

The distribution of immunocytes in the rat uterus undergoes profound changes during early pregnancy. This study was designed to evaluate the respective contributions of hormonal and local factors to regulation of the distribution and number of MCA341+ monocyte-macrophage antigen-bearing cells and T-lymphocyte-polymorphonuclear leukocyte (PMN) antigen-bearing cells before and during implantation of the fertilized ovum. Immunohistological data in normal rat pregnancy were compared to those found in cycling rats, ovariectomized rats, pseudopregnant rats (the oviducts of which had been sectioned on Day 0.5 of pregnancy), and pregnant rats injected with the antiprogesterone RU-486 on Day 0.5 of pregnancy. Four major events were observed: (1) transient accumulation of T-lymphocyte-PMN antigen-bearing cells in the endometrium close to the lumen and occurring only in the pregnant state 12 h after mating; (2) accumulation of an MCA341+ antigen-bearing monocyte-macrophage subset in the uterus, especially the luminal endometrium, 12 h after ovulation in pregnant as well as cycling rats; (3) progressive disappearance of these labeled cells starting 1 day after ovulation in the pregnant and nonpregnant states and influenced by RU-486 injection; (4) relative persistence of labeled cells in the deep endometrium before the implantation of the conceptus--which requires the presence of fertilized ovum in the genital tract. In conclusion, a complex multifactorial and sequential control of the distribution and number of cells bearing MCA341+ monocyte-macrophage or T-lymphocyte antigens appears to be at work before and during implantation of the rat conceptus, and may involve hormonal factors as well as local factors produced by the embryo or trophoblastic cells.

Animals↗
PubMed1991

Complete Freund adjuvant treatment of pregnant females influences resorption rates in CBA/J x DBA/2 matings via progesterone-mediated immunomodulation.

Treatment of pregnant CBA/J females with CFA at day 0.5 and 7.5 of pregnancy significantly reduced the fetal resorption rates from 45% to 29% (P less than 0.05). Supernatants of progesterone-treated spleen cells from CFA treated CBA/J females pregnant of DBA/2 males significantly reduced natural cytotoxicity, while those of untreated identically pregnant mice had no effect. Supernatants of CFA-treated virgin mice blocked natural cytotoxicity to the same extent as those of CFA-treated pregnant mice. These data suggest that nonspecific immunostimulation induces progesterone receptors in spleen cells of CBA mice and that these receptors allow a progesterone dependent suppressive pathway to exert an antiresorptive effect.

Animals↗
PubMed1990

A progesterone-induced blocking factor corrects high resorption rates in mice treated with antiprogesterone.

Earlier we showed that because of the presence of functional progesterone receptors, lymphocytes of healthy pregnant women produced an immunomodulatory protein in the presence of progesterone, whereas those of nonpregnant persons did not. Progesterone-treated murine pregnancy lymphocytes release a similar factor. The present study reveals the biologic significance of this finding. Treatment of BALB/c mice that were 8 days pregnant with a progesterone receptor blocker (RU 486) resulted in 100% resorption of the fetuses. Simultaneous administration of the supernatant from progesterone-treated murine pregnancy spleen cells restored the resorption rate to the original 6% observed in untreated control animals. These data suggest that functional lymphocytic progesterone binding sites are needed for the maintenance of normal pregnancy. Because of the blockage of progesterone receptors and the consequent inability of the lymphocytes to produce the progesterone-induced blocking factor, abortion is initiated by immune factors. The fact that administration of the preformed blocking factor counteracted the effect of antiprogesterone treatment suggests that progesterone-mediated immunosuppression is needed for the maintenance of normal gestation.

Abortion, Induced↗
PubMed1990

Reactivity of lymphocytes to a progesterone receptor-specific monoclonal antibody.

In this study we present evidence for reactivity of pregnancy lymphocytes, but not nonpregnancy lymphocytes, with the progesterone receptor-specific monoclonal antibody mPRI. Using an avidin-biotin peroxidase detection system, we found a nuclear staining in 14.6 +/- 3.7% (mean +/- SEM, N = 27) of pregnancy lymphocytes, while only 0.47 +/- 0.33% (mean +/- SEM, N = 15) of nonpregnancy lymphocytes reacted with the antibody. To characterize the receptor-bearing subset, CD8+ and CD4+ cells were depleted by complement-dependent lysis. Depletion of CD8+ cells was accompanied by 62 +/- 18% loss of progesterone receptor-bearing cells, while depletion of CD4+ cells resulted in a twofold increase in the number of positively staining lymphocytes. In nonpregnancy lymphocytes a 3-day PHA treatment, as well as allogeneic stimulation, resulted in a significant increase in the number of receptor-containing cells. These results suggest that pregnancy, but not nonpregnancy, lymphocytes contain progesterone binding structures, and that these are inducible by mitogenic or alloantigenic stimuli.

Antibodies, Monoclonal↗
PubMed1990

The effects of anti-CD4 and anti-CD8 antibody treatment on placental growth and function in allogeneic and syngeneic murine pregnancy.

During pregnancy, maternal immune recognition of paternal alloantigens has been shown to result in an increased influx of maternal T cells into the spleen, draining lymph nodes and decidua. In previous studies we have shown that polyclonal or monoclonal anti-T cell antibody treatment of allogeneically pregnant mice results in decreased placental proliferation and phagocytosis in vivo. In the present study we compare the effect of such antibody treatment during allogeneic and syngeneic pregnancy. We show that monoclonal anti-CD8 treatment of both types of pregnant females reduces placental proliferation and phagocytosis. Anti-CD4 antibody treatment, on the other hand, only affects placental proliferation, indicating that there is a complex network of immune interactions affecting placental growth and function.

Animals↗
PubMed1990

Lymphocyte-derived progesterone-induced blocking factor corrects resorption in a murine abortion system.

An anti-abortive effect of a progesterone-induced blocking factor has been shown in the CBA/J x DBA/2 abortion system. I.p. injections of pregnant mice on days 7.5, 9.5, and 11.5 of gestation with dialyzed supernatants from progesterone-treated murine pregnancy spleen cells (but not from control ones) significantly (P less than 0.01) reduced the resorption rate from 47.7% in the untreated animals to 20.7%.

Animals↗