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Publications and source records attributed to E Menu.

45 records · Page 3Linked to original sources
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

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

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↗
PubMed1988

[Role of the placenta in maintaining the fetal allograft].

Present knowledge of the alloantigenic status of the placenta, which makes it a natural semi-allogeneic allograft is briefly surveyed. The systemic immunoregulatory mechanisms operating during normal allopregnancy which are not a prerequisite for a successful pregnancy are recalled. The placenta--dependent local mechanisms, e.g. trophoblast dependent decidual suppressor cells, factor mediated and factor independent resistance to cell mediated lysis, are surveyed as well as some of the mechanisms of action of trophoblast regulatory factors, namely suppressor cell induction and inhibition of IL-2 dependent cell growth/activation. The main feature of the CBA x DBA/2 model of spontaneous abortions in mice, and its prevention by anti Balb/c leukocyte immunisation are described. It was shown that anti-T cell depletion prevents the anti-abortive effects of immunisation. Such a treatment is also able to restore normal placental weight in auto-immune MRL lpr mice, which are known to display excess seric CSF beta-like activity (CSFs being in vitro efficient growth factors for trophoblasts). Transfer of such cells into the MHC compatible CBA/J prevents resorbtions upon a subsequent mating with DBA/2. Thus, direct effects of CSFs beta 1 and beta 2 as anti abortifacient (IL3 and GM CSF) are described together with the abortificacient effects of TNFs and NKs activators.

Abortion, Spontaneous↗
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

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↗