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Biomedical subjects

G Chaouat

Publications and source records attributed to G Chaouat.

At least 109 records · Page 6Linked to original sources
PubMed1990

Progesterone suppression of pregnancy lymphocytes is not mediated by glucocorticoid effect.

This study investigated whether the suppressive effect of progesterone on pregnancy lymphocytes is mediated by specific progesterone receptors. The effects of a competitive progesterone antagonist (RU486) and a specific glucocorticoid receptor blocker (RU43044) were tested on the release of a blocking factor by progesterone-treated pregnancy lymphocytes. RU 486 tested at an equal concentration as progesterone significantly inhibited the production of the blocking factor, while RU 43044 was without effect. These data suggest that in pregnancy, lymphocyte progesterone acts on specific progesterone receptors and glucocorticoid binding sites are not involved.

Female↗
PubMed1990

A murine model of NK cell mediated resorption.

There is increasing evidence that some models of immunologically mediated murine embryo demise involve nonspecific lytic effector cells. In this paper, we use two double stranded synthetic RNAs, known as potent interferon inducers and NK cell activators, the Poly (I). Poly (C) and the less toxic Poly (I). Poly (C12U). These polynucleotides enhance fetal resorption rates in both resorption prone and none-resorption prone strains of mice. We have studied the kinetics of the phenomenon, and observed an anti-implantation-like effect of early injection during early pregnancy. The abortifacient effects can be adoptively transferred to naive recipients by spleen cells from Ds RNA injected donors. Such effects are abrogated if the cells are pretreated with anti-NK cell antiserum. The relevance of these findings to the survival of the conceptus is suggested.

Animals↗
PubMed1990

The effect of a progesterone-induced immunologic blocking factor on NK-mediated resorption.

Transfer of spleen cells from poly (I)-poly(C12U)-treated Balb/c mice to 6.5-days-pregnant Balb/c mice significantly increased the resorption rate (P less than 0.01) from 11% to 48%. The supernatant of progesterone-treated spleen cells from pregnant C3H mice abrogated the effect of spleen cell transfer. We conclude that by blocking NK activity in vivo, the progesterone-induced blocking factor favors the maintenance of pregnancy.

Animals↗
PubMed1990

Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy.

In this study, we examined the effect of injecting various cytokines. We report here that tumour necrosis factor (TNF)alpha, gamma-interferon and interleukin 2 (IL-2) can, in some circumstances, increase fetal resorption rates in abortion-prone (CBA/J x DBA/2) and non-abortion prone (CBA/J x BALB/c,C3H x DBA/2) matings: 1000 units TNF enhanced resorptions from 43 to 79% in CBA x DBA/2, from 7 to 89% in CBA x BALB/c, from 5 to 47% in C3H x DBA/2. The effect was both gestational age- and dose-dependent. Gamma interferon and R-IL-2 enhanced resorptions from 38 to 68% and 76% respectively in the CBA/J x DBA/2 mating combination, whereas the rates in CBA/J x BALB/c matings were enhanced from 6 to 44% and 55%. Lipopolysaccharide (LPS), which is known to lead to the release of TNF-alpha, had a similar effect, leading to gestational age- and dose-dependent enhancement of resorptions up to 100%. However, cytokines of the CSF family, including IL-3 and GM-CSF, increased the chances of fetal survival when injected into abortion-prone mice, e.g. reducing resorption rates in the abortion-prone CBA/J x DBA/2 mating combination from 55 to 22% (IL-3), and 47 to 8% (GM-CSF). They also increased fetal and placental weight and, in particular, expanded the spongiotrophoblast zone in the placenta. The latter observations may be due to a direct trophic influence on placental cells, perhaps through a cytokine cascade, or an indirect effect due to inhibition of natural killer (NK)-like cells, or both. Whatever the mechanism, these results may find practical application in influencing reproductive outcome in women and other species.

Animals↗
PubMed1989

Hormone-induced preimplantation Lyt 2+ murine uterine suppressor cells persist after implantation and may reduce the spontaneous abortion rate in CBA/J mice.

Immunoregulatory cells in the maternal uterine endometrium and decidua are thought to play an important role in ensuring the success of the semiallogeneic conceptus. Two phases of suppression have been described in pregnant mice. Prior to implantation, the hormonal changes triggered by mating activate or recruit a population of nonspecific Lyt 2+ suppressor cells that inhibit cytotoxic T lymphocyte generation: this suppression appears to wane at the time or implantation and 4-5 days after implantation, a non-T suppressor cell population activated or recruited by fetal trophoblast cells develops. In this paper we confirm the non-major histocompatibility complex specificity of the hormone-regulated preimplantation suppressor cell. We show that this activity persists in the uterus during the early postimplantation period where its suppressive activity is masked by an Fc-receptor-positive cell population recruited by the implanting embryo. The potential importance of the persisting suppressor cells is suggested by an increase in the rate of spontaneous abortion of DBA2-mated CBA/J mice following injection of monoclonal anti-Lyt 2+ antibody in the early postimplantation period.

Abortion, Veterinary↗
PubMed1989

Immunoactive products of human placenta. I. An immunoregulatory factor obtained from explant cultures of human placenta inhibits CTL generation and cytotoxic effector activity.

Supernatants were prepared from short-duration explant cultures of term human placentas obtained after cesarean delivery. These supernatants inhibited murine and human mixed lymphocyte reactions, as well as CTL generation. The effects were reversed by an excess of IL-2-containing medium. Similarly, the material inhibited human natural killer cytotoxicity against K 562 targets. The material was subjected to gel-filtration chromatography on an ACA 44 or Bio-Gel A15m column. The apparent MW of the MLR-CML material was about 60-70 kDa, whereas the NK inhibiting activity was eluted in high-MW components (greater than 200 kDa) as well as in the 50-kDa range. The relevance of this material in local immunoregulation during human pregnancy is discussed.

Adjuvants, Immunologic↗
PubMed1989

Lack of correlation of immunosuppressive activity secreted by human in vitro fertilized (IVF) ova with successful pregnancy.

The high rate of implantation failure in humans following in vitro fertilization (IVF) has been attributed to a lack of production of immunosuppressive factors by cleaved embryos, rendering them vulnerable to maternal immune attack just before or around implantation. Systemic as well as blastocyst-secreted suppressor factors have been described and claimed to be responsible for successful pregnancy. Experimentally, we have screened in a double-blind fashion the suppressive activity of human embryo culture media (B2 Menezo system, France) in which zygotes after decoronization were individually cultured during 24 hr on lymphocyte proliferation as well as natural killer (NK) activity. Suppressive activity in media from cleaved and uncleaved ova did not differ significantly, and activity in media from transferred embryos was not correlated significantly with successful pregnancy. The implications of these data are discussed.

Analysis of Variance↗
PubMed1989

Immunoregulatory effects of a suppressor factor from healthy pregnant women's lymphocytes after progesterone induction.

Progesterone-treated pregnancy lymphocytes release an immunologic blocking factor. The mode of action of this substance was investigated. The supernatant of progesterone-treated pregnancy lymphocytes was highly suppressive of natural cytotoxicity toward human embryonic fibroblast target cells as well as of natural killer cell activity. The effect was not observed when progesterone induction was performed in the presence of RU 486, a progesterone receptor blocking agent. The factor was able to inhibit mixed lymphocyte reactions (MLRs), and transfer coculture experiments revealed that this effect was dependent on major histocompatibility complex nonspecific, nonrestricted suppressor T cells. The activation/expansion of suppressor inducer and suppressor effector T cells was further proved by fluorescence-activated cell sorter analysis of the populations from MLRs cultured in the presence of the inhibitory factor. These changes were not observed with MLRs performed in the presence of supernatants from progesterone + RU 486-treated peripheral blood lymphocytes. The inhibitory material, on the other hand, did not affect either production or function of IL-2. We conclude that in the presence of high local concentrations of progesterone, a suppressive pathway dependent on specific progesterone-CD8+ lymphocyte interaction might be established. This mechanism might play an important role in the maintenance of pregnancy.

Antibodies, Monoclonal↗
PubMed1989

Immunoactive products of human placenta. II. Direct inhibition of non-MHC restricted cytolytic activity of human CD3 alpha-beta but not CD3 gamma-delta expressing T cell clones.

The effect of human placental supernatant obtained from explant cultures of caesarean delivery placentae was monitored on both alpha-beta human T cell clones, which display both cytotoxic alloreactivity and non-MHC restricted cytotoxicity against K562 target cells, and gamma-delta ones endowed solely with the latter. It was found that, under appropriate experimental conditions, direct inhibition of the cytolytic activity of alpha-beta T cell clones was exerted by the supernatant. In contrast, gamma-delta T cell clones were unaffected. The relevance of these data to the survival of the fetal allograft is discussed.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Lymphocytic progesterone receptors in normal and pathological human pregnancy.

The progesterone receptor-specific monoclonal antibody (MoAb) mPRI was tested for its reactivity towards peripheral blood lymphocytes (PBL) of 49 healthy pregnant women, nine pregnant women with clinical symptoms of threatened preterm delivery, seven women with recurrent spontaneous abortion, ten women in labour and ten women with spontaneous abortion. Lymphocytes of 12 healthy age-matched non-pregnant volunteers were used as controls. Lymphocytes of nine healthy pregnant women at the 1st trimester of pregnancy and those of two non-pregnant donors were tested for the presence of estrogen and progesterone receptors by enzyme immunoassay. PBL of healthy pregnant women contained significantly more positive cells than those of non-pregnant controls. Furthermore, the number of receptor-containing cells increased in parallel with gestational age. In blood samples drawn during labour, as well as in those obtained from women with spontaneous abortion or clinical symptoms of threatened pre-term delivery, the percentage of positively stained lymphocytes was significantly lower than normal pregnancy values. This was also the case in peripheral blood of pregnant women with a history of recurrent spontaneous abortions.

Abortion, Habitual↗
PubMed1989

Progesterone receptors in lymphocytes of liver-transplanted and transfused patients.

Previous data have shown that lymphocytes from pregnant women, but not from non-pregnant individuals, displayed progesterone receptors. These receptors are inducible in normal human lymphocytes in vitro by mitogenic or allogeneic stimuli. The present study was designed to test the role of in vivo allogeneic stimulation in inducing progesterone receptors in lymphocytes from transplanted and transfused patients. Receptors were detected by immunohistology using a progesterone receptor-specific MoAb and avidin-biotin system. Peripheral blood lymphocytes from 56 healthy pregnant women, 8 liver-transplanted patients and 15 transfused patients contained significantly more receptor-positive cells (P less than 0.001) than those of non-pregnant individuals. In transplanted and transfused patients no correlation was found between the percentage of positive lymphocytes and age, sex or transplant survival. Our results show that in these three groups the percentage of receptor-bearing lymphocytes was higher than in normal subjects.

Adult↗
PubMed1989

Effects of lymphokines and immune complexes on murine placental cell growth in vitro.

Isolated murine placental cells obtained at Day 16 of allogeneic gestation (C3H x DBA/2J) were cultured for 3 days alone or in coculture with irradiated mouse splenocytes at the end of which 3H-thymidine was added for an additional 18-h culture to assess cell proliferation. Placental cell proliferation was significantly enhanced at spleen cell:placental cell ratios of 10:1 and 25:1 above that observed in the absence of added spleen cells. The stimulatory effect of irradiated allogeneic (C3H plus Balb/cJ) spleen cell cultures was significantly greater (approximately 2-fold) than that of isogeneic spleen cells (C3H alone). Conditioned medium from murine spleen cells cultured with concanavalin A (ConA) to induce lymphokine production had dose-dependent inhibitory effects on proliferation when added to placental cell cultures over a range of concentrations from 10 to 40% (vol:vol). Addition of pseudo "immune complexes" in the form of heat-aggregated human gamma globulin (AHGG) to culture medium failed to alter placental cell proliferation over a range of concentrations from 2 to 200 micrograms/ml either in the absence or presence of ConA-conditioned medium. In contrast to late-gestational stage placental cells, cell suspensions obtained from Days 8-9 murine ectoplacental cone (EPC) outgrowths, or from earlier stage placentas (Days 12-14) responded to low concentrations of conditioned medium from ConA-stimulated splenocytes with increased proliferation. The effect was less impressive on placental cells at gestational ages later than 12 days than on earlier stage preparations. On all placental cell suspensions tested, as well as EPC cells, a clear-cut inhibition of growth was observed at high doses of conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Cells bearing granulocyte-macrophage and T lymphocyte antigens in the rat uterus before and during ovum implantation.

There is little detailed information on the distribution of granulocytes-macrophages and lymphocytes at the pre- and peri-implantation period of the embryo in the uterus. Using two monoclonal antibodies (MAS-099C and MRC-OX41) we found that cells labelled with antibodies specific to either T lymphocytes and thymocytes or granulocytes-macrophages were present in the endometrium and myometrium before ovum implantation. Both types of labelled cells appeared to migrate from the uterine lumen to the deep endometrium, where their number peaked on day 4. At the early implantation period (days 5 to 7), there was a total lack of labelled cells around the conceptus. Specific changes before ovum implantation in the distribution or activation state of T lymphocytes and granulocyte macrophages may favour early embryo acceptance.

Animals↗
PubMed1988

Vaccination against spontaneous abortion in mice by preimmunization with an anti-idiotypic antibody.

CBA/J females mated with DBA/2 display a high level of fetal wastage which can be corrected by anti-Balb/c vaccination. A batch of CBA/J anti-(CBA/J anti-Balb/c) antiserum was raised. This serum was characterized as anti-idiotypic by various techniques, including a solid-phase radioimmunoassay. Such a serum proved to confer protection against resorptions when injected into CBA/J mice mated with DBA/2. However, the kinetics of the effect pointed to the need for administration in early pregnancy for successful protection. The significance of these data, and the possible mechanism(s) by which the serum acts, are discussed.

Abortion, Spontaneous↗