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Cytokine interactions between the maternal immune and reproductive systems
The Scientific & Social Program: Vth ISDCI Congress E1
$63
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CYTOKINE INTERACTIONS BETWEEN REPRODUCTIVE SYSTEMS. Thomas G. Wegmann. University of Alberta, 8-65 Medical Sciences T6G 2H7 Canada
THE M A T E R N A L IMMUNE AND Department of Immunology, Building, Edmonton, Alberta
Although a number of recent experiments indicate that an intact immune system is not necessary for successful reproduction, other experiments indicate that it definitely plays a role in enhancing reproductive success. The clearest example comes from mice in which spontaneous fetal resorption can be prevented by immunizing with paternal alloantigens. By now this result has been generalized to a number of different mouse strains and antigenically the effect has been pinned down to individual class I and class II MHC antigens. The destructive effect seems to be mediated by NK-like cells and cytokines including TNF-alpha. Antagonistic to these cytokines are the CSF family, including GM-CSF, IL-3, and CSF-1. These have been found to be trophoblast growth factors and have also been found to be secreted locally during pregnancy, in some cases under hormonal influence. GM-CSF is of particular interest because there appears to be tissue-specific cytokine expression in the placenta. There is also evidence accumulating that GM-CSF plays a role in altering trophoblast membrane function and also in stimulating the production of certain reproductive endocrines such as human placental lactogen and human chorionic gonadotropin. The implications of these recent developments on communication between the maternal immune and reproductive systems will be reviewed in detail.
E2 THE IMMUNE RESPONSE OF OFFSPRING MICE FROM MOTHERS IMMUNIZED DURING PREGNANCY WITH PROTEIN ANTIGENS. *A. Malley. immunology Dept,, Oregon Regional Primate Research Center~ Beaverton, OR 97006, USA. The immune system of offspring mlce from mOthers with photo-oxldlzed timothy grass pollen antigen B (OX-AgB) or Trinltrophenyl-bovlne gamma globulln (TNPBGG) during their pregnancy was examined. O f f s p r l ~ mice ~,-,unlzed 6 or 8 weeks after d e l l v e r y w l t h the same antigen administered to their mothers have completely suppressed primary responses and > 80Z suppressed secondary responses. The observed Immunosuppresslon in offspring mice persists for 16 weeks after delivery, and is antigen specific. Adoptive transfer experiments show that spleen cells from adult OX-AgB primed mice injected i.v. into lethally X-irradlated (800 fads) syngenelc recipients and challenged with antigen produce significant levels of AgB-speclflc lEG antibody. Spleen cells (5 x 106) from offspring mice of mothers immunlzed with OX-AgB during their pregnancy were added to spleen cells from adult OX-AEB primed mlce and injected i.v. into lethally X-lrradlated recipients and challenged with antigen. These recipients showed a significantly (> 85Z) Immunosuppressed secondary response. The observed suppression is mediated by T cells, and treatment of these T cells with anti-CD4 and anti-CD8 antibodies and complement demonstrated that both CD4 and CD8 T cells were needed to mediate the observed suppression. The reported findings are discussed in relation to possible mechanisms of fetal tolerance.
$63
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CYTOKINE INTERACTIONS BETWEEN REPRODUCTIVE SYSTEMS. Thomas G. Wegmann. University of Alberta, 8-65 Medical Sciences T6G 2H7 Canada
THE M A T E R N A L IMMUNE AND Department of Immunology, Building, Edmonton, Alberta
Although a number of recent experiments indicate that an intact immune system is not necessary for successful reproduction, other experiments indicate that it definitely plays a role in enhancing reproductive success. The clearest example comes from mice in which spontaneous fetal resorption can be prevented by immunizing with paternal alloantigens. By now this result has been generalized to a number of different mouse strains and antigenically the effect has been pinned down to individual class I and class II MHC antigens. The destructive effect seems to be mediated by NK-like cells and cytokines including TNF-alpha. Antagonistic to these cytokines are the CSF family, including GM-CSF, IL-3, and CSF-1. These have been found to be trophoblast growth factors and have also been found to be secreted locally during pregnancy, in some cases under hormonal influence. GM-CSF is of particular interest because there appears to be tissue-specific cytokine expression in the placenta. There is also evidence accumulating that GM-CSF plays a role in altering trophoblast membrane function and also in stimulating the production of certain reproductive endocrines such as human placental lactogen and human chorionic gonadotropin. The implications of these recent developments on communication between the maternal immune and reproductive systems will be reviewed in detail.
E2 THE IMMUNE RESPONSE OF OFFSPRING MICE FROM MOTHERS IMMUNIZED DURING PREGNANCY WITH PROTEIN ANTIGENS. *A. Malley. immunology Dept,, Oregon Regional Primate Research Center~ Beaverton, OR 97006, USA. The immune system of offspring mlce from mOthers with photo-oxldlzed timothy grass pollen antigen B (OX-AgB) or Trinltrophenyl-bovlne gamma globulln (TNPBGG) during their pregnancy was examined. O f f s p r l ~ mice ~,-,unlzed 6 or 8 weeks after d e l l v e r y w l t h the same antigen administered to their mothers have completely suppressed primary responses and > 80Z suppressed secondary responses. The observed Immunosuppresslon in offspring mice persists for 16 weeks after delivery, and is antigen specific. Adoptive transfer experiments show that spleen cells from adult OX-AgB primed mice injected i.v. into lethally X-irradlated (800 fads) syngenelc recipients and challenged with antigen produce significant levels of AgB-speclflc lEG antibody. Spleen cells (5 x 106) from offspring mice of mothers immunlzed with OX-AgB during their pregnancy were added to spleen cells from adult OX-AEB primed mlce and injected i.v. into lethally X-lrradlated recipients and challenged with antigen. These recipients showed a significantly (> 85Z) Immunosuppressed secondary response. The observed suppression is mediated by T cells, and treatment of these T cells with anti-CD4 and anti-CD8 antibodies and complement demonstrated that both CD4 and CD8 T cells were needed to mediate the observed suppression. The reported findings are discussed in relation to possible mechanisms of fetal tolerance.