asialo-gm1-ganglioside and Fetal-Resorption

The paradigm of local suppression necessary to understand the survival of the fetal allograft is often compared with the host-tumor relationship.. We investigated two components of local immune suppression: placenta-induced immunosuppression, which is mediated at least in part by a soluble factor of low molecular weight that can induce anergy in lymphocytes, and interleukin-10 (IL-10).. We show that enhancement of IL-10 production in the decidua and placenta after alloimmunization requires the presence of Asialo GM1+ cells. Placenta-induced immunosuppression is linked with defects in phosphorylation of some components of the T cell receptor.. NK cells could be in fact regulatory cells pushing maternal immune response toward a Th2 profile, beneficial for fetal survival, or toward a Th1 type of immune response, which acts in synergy. Modulation of TcR may represent a new mechanism for maternal-fetal tolerance.

Topics: Animals; Clonal Anergy; Crosses, Genetic; Female; Fetal Resorption; Fetus; G(M1) Ganglioside; H-2 Antigens; History, 20th Century; Humans; Immune Tolerance; Interleukin-10; Killer Cells, Natural; Lymphokines; Mice; Mice, Inbred Strains; Models, Immunological; Models, Molecular; Pregnancy; Recombinant Proteins; Th1 Cells; Th2 Cells

Topics: Abortion, Spontaneous; Adjuvants, Immunologic; Animals; Female; Fetal Resorption; Fetus; G(M1) Ganglioside; Glycosphingolipids; Humans; Immunity, Innate; Interferon Inducers; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Models, Biological; Pregnancy; Tumor Necrosis Factor-alpha

Topics: Abortion, Spontaneous; Animals; Crosses, Genetic; Female; Fetal Death; Fetal Resorption; G(M1) Ganglioside; Glycosphingolipids; Humans; Immunization; Lymphocytes; Mice; Mice, Inbred Strains; Models, Biological; Muridae; Pregnancy; Research Design; Species Specificity; Tumor Necrosis Factor-alpha

Stress adversely affects pregnancy outcome and has been implicated as an abortogen in both animals and humans. However, the mechanisms whereby stress aborts are largely unknown. Alloimmunization can prevent stress-triggered abortion, and immunization is known to increase transforming growth factor-beta 2 (TGF-beta 2)-related suppressive activity.. To investigate these mechanisms, DBA/2J males were mated to CBA/J or C3H/HeJ females, and the pregnant females were exposed to ultrasonic sound stress for a period of 24 h between day 4.5 to 8.5 of pregnancy.. Ultrasonic stress significantly elevated the resorption rate with a peak effect on day 5.5 in the CBA/J females and on day 4.5 in the LPS-resistant C3H/HeJ females. The tumor necrosis factor-alpha (TNF-alpha) release from the decidua was also elevated and the TGF-beta 2-mediated suppressive activity was significantly decreased. The resorption rate only increased when the TNF-alpha/TGF-beta 2 ratio was increased compared to the control.. These data suggest that stress may inhibit protective suppressor mechanisms and promote secretion of abortogenic cytokines such as TNF-alpha. Possible mechanisms are discussed.

Topics: Abortion, Spontaneous; Animals; Decidua; Disease Models, Animal; Female; Fetal Resorption; G(M1) Ganglioside; Immunization; Isoantigens; Male; Mice; Mice, Inbred Strains; Noise; Pest Control; Pregnancy; Pregnancy Complications; Psychoneuroimmunology; Stress, Physiological; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Ultrasonics

Partial resorption or abortion (depending upon the stage of gestation) can be induced with lower doses of lipopolysaccharide (LPS) (DIFCO) and human R-TNF than previously demonstrated. As can be expected, the abortion-prone CBA x DBA/2 and B10 x B10.A mating combinations are the most sensitive to such low doses. LPS synergizes with low doses of IL-2, gamma interferon, poly(I).poly(C) 12U. Treatment by GM-CSF, IL-3, or anti-natural killer antiserum decreases both TNF levels and abortion rates. Similar prevention of induced resorptions are obtained with either a neutralizing polyclonal rabbit anti-TNF antiserum or with pentoxyfilline, which has been shown to reduce resorption rates in CBA x DBA/2 pregnancies. More important, abortions induced by low doses of LPS or R-TNF can be prevented by alloimmunization. During late gestation, on the contrary, LPS- or TNF-induced delivery cannot be counteracted by alloimmunization nor by a progesterone-induced blocking factor, at least in the regimens employed by us. Therefore, although resorptions and parturition share common pathways consisting of immune mediators, they are not regulated similarly by the maternal immune system.

Topics: Abortifacient Agents; Animals; Dose-Response Relationship, Drug; Drug Synergism; Female; Fetal Resorption; G(M1) Ganglioside; Granulocyte-Macrophage Colony-Stimulating Factor; Interferon-gamma; Lipopolysaccharides; Mice; Mice, Inbred Strains; Pregnancy; Pregnancy, Animal; Progesterone; Recombinant Proteins; Tumor Necrosis Factor-alpha

Spontaneous resorption (abortion) that occurs at a high rate in DBA/2-mated CBA/J female mice is dependent upon asialoGM1+ natural effector-type cells, can be ameliorated by alloimmunization or administration of GM-CSF, and is augmented by in vivo injection of anti-CD8 antibody. The abortion rate was similarly augmented by administration of monoclonal anti-GM-CSF neutralizing antibody, but the GM-CSF physiologically active in preventing abortion during normal pregnancy did not appear to be derived from maternal CB8+ T cells putatively responding to antigens on the fetoplacental unit. Rather, depletion of CD8+ cells in vivo prevented GM-CSF from reducing the rate of resorptions. GM-CSF administration rapidly downregulates natural effector cells able to kill a trophoblast target cell line in vitro, and anti-CD8+ antibody boosts total splenic cytotoxic cell activity. Further, anti-CD8 completely abrogated the ability of GM-CSF to suppress anti-trophoblast killer cell activity. These cells are known to be asialoGM1+ and injection of anti-asialoGM1 reduced the abortion rate appropriately in mice that had received anti-CD8. These data suggest that GM-CSF acts indirectly to prevent abortion in DBA/2-mated CBA/J mice through a mechanism that requires CD8+ maternal T cells, and systemic regulation of the level of anti-trophoblast killer cell activity may determine the success or failure of pregnancy in this system.

Topics: Abortion, Spontaneous; Animals; Antibodies; CD8 Antigens; Cytotoxicity, Immunologic; Female; Fetal Resorption; G(M1) Ganglioside; Granulocyte-Macrophage Colony-Stimulating Factor; Immune Tolerance; Killer Cells, Natural; Male; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Pregnancy; T-Lymphocyte Subsets; Trophoblasts