Search PubMed⌕ Search

Biomedical subjects

G Chaouat

Publications and source records attributed to G Chaouat.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1987

Local active suppression and successful vaccination against spontaneous abortion in CBA/J mice.

We report here that vaccination of CBA/J female mice with DBA/2 X BALB/c recombinant line that decreases the spontaneous abortion rate increases local active decidua-associated suppressor cell activity. In contrast, vaccination with a recombinant line that increases the abortion rate decreases suppressor cell activity. No correlation was seen between the effect on the abortion rate and the ability of cells from the fetoplacental unit to inhibit cytolysis by NK cells. Successful vaccination against spontaneous abortion may act primarily by augmenting suppressor cell activity in the decidua at the implantation site.

Abortion, Habitual↗
PubMed1987

Immunological and para-immunological mechanisms in spontaneous abortion: recent insights and future directions.

Unexplained spontaneous abortion in humans is currently thought to be related to genetic or immunologic factors. Animal models of spontaneous abortion have been used to try to gain some insight into the problems in humans. From studies of animal models there is increasing evidence that a variety of mechanisms may initiate pregnancy failure and participation of immunologic effectors may be a secondary event. Recent studies indicate that murine abortion that occurs spontaneously (without deliberate immunization by the investigator) may be initiated by para-immunologic host effector cells such as NK cells, macrophages and their toxins that possess selective toxicity which is not antigen-specific. The potential importance of local non-specific suppressive mechanisms in the uterus is also highlighted by their ability to block non-specific para-immune effector cell activation, and by their potential relationship to growth factors in decidual supernatants that promote placental cell growth in vitro. Levels of non-specific suppression do not appear low when fetal death can be attributed to a genetic mutation. The concept that different tissue components of the feto-placental unit serve as targets of different immunologic and para-immunologic effectors is defined. The new insights into the pathophysiology of murine abortion and its correction can provide a useful framework for further analysis of the role of para-immunologic effector mechanisms in unexplained abortion in humans and in non-murine veterinary conditions.

Abortion, Spontaneous↗
PubMed1987

Placental immunoregulatory factors.

Local immune suppression appears to be a key feature in the success of the fetal allograft. Various placental factors have been described endowed with immunoregulatory activity. Much of the available evidence concerning the biological function and biochemical characteristics of these molecules is reviewed here, as well as the controversial issues surrounding them. In the final section, some outstanding questions relating to these immunoregulators are considered.

Animals↗
PubMed1987

Working principles in the immune system implied by the "peptidic self" model.

The hypothesis that self as well as foreign proteins are processed into peptides and presented by major histocompatibility complex antigens leads to a set of working principles that could govern cellular interactions in immune responses. In particular, "idiopeptides," derived from immunoglobulins and T-cell receptors and recognized by appropriate T cells, are expected to play an important regulatory role. We show here that these speculations fit into a consistent view of the immune system.

Animals↗
PubMed1986

Characterization of the cellular basis for the inhibition of cytolytic effector cells by murine placenta.

Direct suppression of cytolytic effector cell function by cells of the placenta may represent one mechanism that protects the "fetal allograft" from rejection by maternal transplantation immunity. Collagenase disaggregated murine placental cells block target cell lysis by natural killer, lymphokine-activated killer, and (CTL)-type killer cells. This inhibition is reversible and noncompetitive, similar to a previously described inhibitor of CTL found in spleens of mice undergoing an acute graft vs host (GVH) response. Velocity sedimentation separation of placental cells shows that the inhibitory activity is primarily associated with cells that cosediment with nucleated fetal erythrocytes. When these erythrocytes were lysed, an increased number of non-erythrocytic cells could be separated and under this circumstance, inhibitory activity was seen in association with either small white cells or fetal erythrocytes and with large white cells. There may be several cell populations in murine placenta that can inhibit cytolytic effector cells. The possible relevance of direct placental inhibition of cytolytic effectors to protection of the "fetal allograft" is discussed.

Animals↗
PubMed1986

Immunogenetic studies of spontaneous abortion in mice. II. Antiabortive effects are independent of systemic regulatory mechanisms.

CBA/J females (H-2k) mated with DBA2/J males (H-2d) exhibit a high rate of fetal resorption. Fetal survival has been improved by pretreatment of CBA/J females with spleen cells from BALB/c J (H-2d) (but not from CBA/J or DBA/2/J) males. Similarly, three out of nine recombinant inbred strains (recombining BALB/c and DBA2 genomes at the homozygous state) possess antiabortive effects like the BALB/c parent. Previous studies showed that BALB/c pretreatment triggers the appearance of suppressor cells in the spleen and of IgG1 anti-H-2d antibodies in the serum of CBA/J females. Studies of these two immunological parameters after CBA/J preimmunization by the different recombinant strains suggest that local intrauterine immunoregulation is the determinant of success or failure of allopregnancy.

Abortion, Veterinary↗
PubMed1986

Immunoactive products of placenta. V: Soluble factors from murine placenta can block effector stages of maternal antipaternal cell-mediated immunity.

Supernatants from short-term cultures of placental or trophoblast-enriched cell suspensions derived from 14-17-day isopregnant mice display suppressive activity on NK lysis in vitro. The soluble factor is produced by trypsin-sensitive cells and requires protein synthesis. Its activity is destroyed by treatment with insoluble trypsin. The suppression is not strain restricted, but appears species-restricted. The factor acts at the level of the NK effectors themselves. Furthermore, such supernatants also are able to inhibit CTL-mediated lysis at the effector stage, in an MHC nonrestricted, nonspecific fashion. The effect is not seen with supernatants from control fetal tissues. At least two mechanisms could be involved: inhibition of homing toward allogeneic targets, and a direct effect on effector cell lytic action. These factors could play an important role in protecting the placenta from the deleterious effects of maternal antipaternal immunity and could explain the survival of the fetus in a presensitized maternal host.

Animals↗
PubMed1986

Immune presensitization and local intrauterine defences as determinants of success or failure of murine interspecies pregnancies.

Putatively immuno-incompetent Mus musculus females exhibited failure to support pregnancy of Mus caroli embryos. These results for M. musculus females (i.e. treated by cyclosporine A, of the nu/nu genotype, and as an interspecies chimaera) can be explained in immunological terms. Mus musculus females possessed pre-sensitized cytotoxic T cells against Mus caroli antigen. Nu/nu mice possessed activated NK cells and macrophages, and selectively discriminated against Mus caroli embryos early in pregnancy unlike normal +/+ females; the requirement for T cells to activate non-specific cytotoxic effector mechanisms was bypassed in nu/nu mice. Mus caroli are not inbred, and interspecies chimaeras which are tolerant of the antigens on the Mus musculus donor strain were not tolerant of cells from unrelated Mus caroli. Interspecies chimaeras also behaved as if they were pre-sensitized to Mus caroli. Our results show that Mus caroli embryos recruit fewer active suppressor cells even when gestating in Mus caroli decidua as compared to Mus musculus embryos in Mus musculus decidua and that the ability of Mus caroli placental cells to directly inhibit cytotoxic effector cell killing was inherently less than the inhibitory activity of placental cells from Mus musculus. Mus caroli embryos therefore appear to be less well defended against maternal immune attack even when gestating in a uterus possessing compatible Mus caroli decidual tissue.

Animals↗
PubMed1985

Immunoactive products of placenta: VIII. Translation products of messenger RNA extracted from murine placenta or A6B9IC5 teratocarcinoma are immunosuppressive in vitro.

RNA was extracted from placentae of synpregnant C3H mice (day 14 of gestation) and from A6B9IC5 teratocarcinoma. After isolation of poly-(A)+ RNA on an oligo d(T) cellulose column, putative messenger RNA was injected into Xenopus laevi oocytes. Supernatants and homogenates from the oocytes were assayed for immunoregulatory activity in MLR, CML, and NK assays and found to be immunosuppressive. These data indicate that immunomodulators could be obtained from the placenta by molecular biology technology in sufficient quantities for eventual clinical applications.

Animals↗
PubMed1985

Immunoactive products of placenta. IV. Impairment by placental cells and their products of CTL function at effector stage.

Trophoblast-enriched cell suspensions prepared by collagenase digestion from midterm murine placentae were found resistant to CTL-mediated lysis. Treatment of such cells by trypsin or neuraminidase rendered these cells susceptible to such lytic effectors. Collagenase-prepared cell suspensions could impair CTL action, whereas neuraminidase- or trypsin-treated cells did not retain this property. This effect was also observed with extracts. These results indicate that soluble factors (which we will characterize in another paper) released by trophoblast cells (in fact, spongiotrophoblast) can interfere in a dose-dependent fashion with the action of lytic effectors. We suggest that such active mechanisms are physiologic components of the placental barrier and might be defective in some cases of immunologic abortions.

Animals↗
PubMed1985

Selection of BW 5147 subclones devoid of non-specific suppressive activity for use in cell hybridization.

Culture supernatants of BW 5147 cells widely used for T-cell hybridization often manifest non-MHC-restricted, non-antigen-specific regulatory activities on the mixed lymphocyte reaction (MLR) of mouse cells. This report demonstrates that, whereas supernatants of BW 5147 cells grown at low concentrations (2 X 10(5)/ml) enhanced MLR, high cell concentration (2 X 10(6)/ml) supernatants markedly inhibited this reaction. BW 5147 cell-free extracts significantly inhibited MLR and in vitro antibody production (PFC), as well as the mitogenic response to lipopolysaccharide E. coli (LPS) of mouse spleen cells, but did not affect the response to an optimal dose of phytohaemagglutinin (PHA). Both supernatant and cell-free extract inhibitory activities were located in 60,000 MW fraction. Inhibitory material of low MW (less than 12,000) was also found in high cell concentration supernatants. A similar suppressive activity was exerted by cell-free extracts of P3 X 63 NS cells used for B-cell hybridization. The suppressive activity seemed to stem from some kind of interaction between BW 5147 cells and the fetal calf serum (FCS) of the culture medium. Supernatants from subclones of BW 5147 cells obtained in selected batches of FCS and maintained in the same serum, even at high cell concentrations, did not affect MLR, whereas the supernatants from the same subclones maintained in other batches definitely suppressed this reaction. Thus, provided that culture conditions are chosen carefully, subclones of BW 5147 devoid of effect on in vitro immune reactions can be obtained.

Animals↗
PubMed1985

Immunologic consequences of vaccination against abortion in mice.

CBA/J female mice have a high rate of fetal resorption when mated with DBA/2J males. This fetal wastage can be dramatically reduced by immunizing the female with BALB/cJ but not DBA/2J spleen cells. We report here that immunization with BALB/cJ (but not DBA/2J) spleen cells leads to 1) anti-paternal MHC antibody that is predominantly of the IgG1 isotype, and which disappears from the serum during pregnancy; 2) increased active suppression in both the spleen and placenta; and 3) an ability to adoptively transfer the fetal protection and placental suppression with serum from the immunized mice. Congenic absorption studies before adoptive transfer indicate that the active component of the serum is also directed against the paternal MHC haplotype. These results indicate that maternal humoral immunity can lead to increased fetal protection in correlation with local active suppression in the placenta. They also suggest an expansion of the placental immunoabsorbent hypothesis to include the induction of active suppression against maternal cell-mediated immunity.

Animals↗
PubMed1985

Immunogenetic studies of spontaneous abortion in mice. Preimmunization of females with allogeneic cells.

CBA females (H-2k) mated with DBA2 males (H-2d) exhibit a high rate of fetal resorption (30%) when compared with the CBA female BALB/c male, CBA female/CBA male, DBA2 female/CBA male, DBA2 female/DBA2 male combinations (6 to 8%). Preimmunization of CBA females with spleen cells from DBA2, BALB/c, or CBA males were performed in order to test their effects on CBA maternal tolerance of (CBA X DBA2)F1 fetuses. Only preimmunization with BALB/c male cells was effective in decreasing resorption; cells from BALB/c females had no effect. In order to further test 1) the role of non-MHC-encoded antigens present in the BALB/c male background, 2) the necessity of an additional H-2 difference, and 3) whether or not the phenomenon is H-2d restricted, preimmunizations were performed by using cells from congenic BALB/k (H-2k), BALB/b (H-2b), or BALB/c (H-2d). Only the latter treatment was efficient, which suggests that the paternal H-2d haplotype must be presented in synergy with some non-MHC-encoded antigens in the BALB/c male background. Immunogenetic studies with cells from nine recombinant inbred strains that reassorted DBA2 and BALB/c genomes showed that three of them behave like BALB/c and six like DBA2. This would suggest that the genetic determinism of this phenomenon is simple.

Abortion, Spontaneous↗
PubMed1984

Immunoactive products of placenta. III. Suppression of natural killing activity.

Placental and trophoblast-enriched cells from iso or allopregnant mice (14 to 17 days of gestation) strongly suppress natural killing by mouse splenocytes. The suppression is not strain restricted and acts at the level of the effector cell. It was not reduced by pretreatment of trophoblast cells with RNA and protein synthesis inhibitors, nor by prostaglandin synthetase inhibitors. However, treatment with trypsin abolished the suppressive activity. Because CTL and ADCC cytotoxicity were also inhibited by trophoblast cells at the effector stage, we postulate that trophoblast cells in vivo are endowed with the ability to inactivate various types of cytotoxic cells in their vicinity that are potentially harmful for the conceptus.

Animals↗
PubMed1983

Characterization of T-cell-soluble factors modulating the expression of Ia and H-2 antigens on BALB/c B lymphoma cell lines.

The effect of supernatants of concanavalin A-activated spleen cells (CAS) on the expression of various antigens, especially Ia antigens, on BALB/c B lymphoid cells, was examined. This study demonstrates the following: (i) CAS enhanced the expression of Ia antigens on four out of five BALB/c lymphoid cell lines. (ii) CAS selectively modulates the expression of Ia and H-2D, but not sIgM or viral gp70 expression, on X16C 8.5 tumor cells. The enhanced levels of Ia expression on B lymphoid tumor cells were also detected by using anti-Ia monoclonal antibodies. (iii) The molecular weight of soluble factor(s) affecting Ia and H-2 was approximately 40,000 estimated by gel filtration on a Sephadex G-200 column. (iv) Type 1 interferon but not interleukin 1, interleukin 2, or T-cell-replacing factor enhanced the expressions of Ia and H-2D antigens. (v) The activity of CAS-modulating Ia and H-2 antigens was eliminated by acidic treatment. It was concluded from this study that at least one of the factor(s) in CAS, modulating the antigenic expression of B-lymphoid cells, was interferon-like in nature. From our findings, a possible immunoregulatory mechanism by interferon was suggested: T cells, after stimulation of mitogens or antigens, secrete interferons which modulate the expression of Ia and H-2 on B cells. Then B cells, whose Ia and H-2 were modulated selectively by T-soluble factors(s), might interact with T cells much more efficiently.

Animals↗
PubMed1983

Vaccination against spontaneous abortion in mice.

We report here that the high rate of spontaneous resorption observed in CBA/J female mice mated with DBA/2 J males can be dramatically reduced by vaccination with Balb/c male spleen cells, but not by CBA/J or DBA/2 J male spleen cells. This effect correlates with the differential ability of Balb/c spleen cells to induce MLR suppressor activity in CBA/J female mice, and should lead to a better understanding of the immunology of the materno-fetal relationship.

Abortion, Habitual↗