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Zentralbl Gynakol 2001; 123(11): 609-618
DOI: 10.1055/s-2001-19514
Übersicht

© Georg Thieme Verlag Stuttgart · New York

Die Rolle der Zytokine an der fetomaternalen Grenze

The role of cytokines at the fetomaternal interfaceK. Geis, J. Dietl
  • Frauenklinik der Bayerischen Julius-Maximilians-Universität Würzburg
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Publication History

Publication Date:
14 January 2002 (online)

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Zusammenfassung

Für das Überleben des semiallogenen Embryos im maternalen Organismus sind verschiedene Mechanismen notwendig. Neben dem Fehlen der klassischen MHC-Klasse-I- und -II-Antigenen auf dem Trophoblasten, kommt vor allem den Zytokinen an der fetomaternalen Grenzzone eine große Bedeutung zu. Eine Vielzahl an Zytokinen reguliert die immunologischen Prozesse, wobei besonders dem Th1/Th2-Gleichgewicht eine entscheidende Rolle zugesprochen wird. Außerdem besteht an der fetomaternalen Grenzzone im Gegensatz zum peripheren Blut eine veränderte Zusammensetzung an immunkompetenten Zellen. Zahlreiche Wechselwirkungen bestehen auch zwischen dem endokrinen und dem Immunsystem, indem verschiedene Hormone modulierend auf die Sekretion der einzelnen Zytokine wirken. Im Bereich der Reproduktionsmedizin ist die Aufklärung dieser Funktionen von großem Interesse, um zukünftig möglicherweise Störungen vor allem in der Frühschwangerschaft behandeln zu können.

The role of cytokines at the fetomaternal interface

Summary

Various mechanisms are necessary for regulating the survival of the semiallogenic embryo in the maternal organism. In addition to the lack of classical MHC class I and II antigens at the trophoblast the cytokines play an important role at the fetomaternal interface. Different cytokines regulate the immunological processes with an emphasis on the Th1/Th2 balance. In contrast to the peripheral blood there is a certain composition of immune competent cells at the fetomaternal interface. There are many different interactions between the endocrine and immunological system. Hormones modulate the secretion of certain cytokines and vice versa. In reproductive medicine it is of specific interest to evaluate these functions for treating problems during the early pregnacy.

Schlüsselwörter

Zytokine - Plazenta - Th1/Th2 - Schwangerschaft - Hormone

Key words

Cytokines - placenta - Th1/Th2 - pregnancy - hormones

Literatur

  • 1 Arck P, Dietl J, Clark D. From the decidual cell internet: trophoblast-recognizing T cells.  Biol Reprod. 1999;  60 227-233
    PubMedGoogle Scholar
  • 2 Athanassakis I, Bleackley R C, Paetkau V, Guilbert L, Barr P J, Wegmann T G. The immunostimulatory effect of T cells and T cell lymphokines on murine fetally-derived placental cells.  J Immunol. 1987;  138 37-44
    PubMedGoogle Scholar
  • 3 Bry K, Hallman M. Transforming growth factor-β2 prevents preterm delivery induced by interleukin-1α and tumor necrosis factor-α in the rabbit.  Am J Obstet Gynecol. 1993;  168 1318-1322
    PubMedGoogle Scholar
  • 4 Bryant-Greenwood G D, Schwabe C. Human relaxins: Chemistry and biology.  Endocr Rev. 1994;  15 5-26
    CrossrefPubMedGoogle Scholar
  • 5 Chaouat G, Menu E, Clark D A, Dy M, Minkovsky M, Wegmann T G. Control of fetal survival in CBA × DBA/2 mice by lymphokine therapy.  J Reprod Fertil. 1990;  89 447-458
    CrossrefPubMedGoogle Scholar
  • 6 Daynes R A, Meikle A W, Araneo B A. Locally active steroid hormones may facilitate compartmentalization of immunity by regulating the types of lymphokines produced by helper T cells.  Res Immunol. 1991;  142 40-45
    PubMedGoogle Scholar
  • 7 Delassus S, Coutinho G C, Saucier C, Darche S, Kourilsky P. Differenzial cytokine expression in maternal blood and placenta during murine gestation.  J Immunol. 1994;  152 2411-2420
    PubMedGoogle Scholar
  • 8 Dietl J, Horny H P, Ruck P, Marzusch K, Kaiserling E, Gries-ser H, Kabelitz D. Intradecidual T lymphocytes lack immunohistochemically detectable T-cell receptors.  Am J Reprod Immunol. 1990;  24 33-36
    PubMedGoogle Scholar
  • 9 Dietl J, Ruck P, Norny H P, Handgretinger R, Marzusch K, Ruck M, Kaiserling E, Griesser H, Kabelitz D. The decidua of early human pregnancy: Immunohistochemistry and function of immunocompetent cells.  Gynecol Obstet Invest. 1992;  33 197-204
    PubMedGoogle Scholar
  • 10 Garcia-Lloret M I, Morrish D W, Wegmann T G, Honore L, Turner A R, Guilbert L J. Demonstration of functional cytokine-placental interactions: CSF-1 and GM-CSF stimulate human cytotrophoblast differentiation and peptide hormone secretion.  Exp Cell Res. 1994;  214 46-54
    CrossrefPubMedGoogle Scholar
  • 11 Geiselhart A, Dietl J, Marzusch K, Ruck P, Ruck M, Horny H P, Kaiserling E, Handgretinger R. Comparative analysis of the immunophenotypes of decidual and peripheral blood large granular lymphocytes and T cells during early human pregnancy.  Am J Reprod Immunol. 1995;  33 315-322
    PubMedGoogle Scholar
  • 12 Gobin S J, Wilson L, Keijsers V, Van den Elsen P J. Antigen processing and presentation by human trophoblast-derived cell lines.  J Immunol. 1997;  158 3587-3592
    PubMedGoogle Scholar
  • 13 Handwerger S. A critical role for interleukin-1(IL-1) and the type 1 IL-1 receptor in blastocyst implantation.  Endocrinology. 1994;  134 519-520
    CrossrefPubMedGoogle Scholar
  • 14 Hu X L, Yang Y, Hunt J S. Differenzial distribution of interleukin-1α and interleukin-1β proteins in human placentas.  J Reprod Immunol. 1992;  22 257-268
    PubMedGoogle Scholar
  • 15 Jacobs R, Stoll M, Stratmann G, Leo R, Link H, Schmidt R E. CD16-CD56+ natural killer cells after bone marrow transplantation.  Blood. 1992;  79 3239-3244
    PubMedGoogle Scholar
  • 16 Jokhi P P, King A, Sharkey A M, Smith S K, Loke Y W. Screening for cytokine messenger ribonucleic acids in purified human decidual lymphocyte populations by the reverse-transcriptase polymerase chain reaction.  J Immunol. 1994;  153 4427-4435
    PubMedGoogle Scholar
  • 17 Kämmerer U, Schoppet M, McLellan A D, Kapp M, Huppertz H I, Kämpgen E, Dietl J. Human decidua contains potent immunostimulatory CD83+ dendritic cells.  Am J Pathol. 2000;  157 159-169
    PubMedGoogle Scholar
  • 18 Kelly R W, Critchley H O. A T-helper-2 bias in decidua: the prostaglandin contribution of the macrophage and trophoblast.  J Reprod Immunol. 1997;  33 181-187
    PubMedGoogle Scholar
  • 19 King A, Wooding P, Gardner L, Loke Y W. Expression of perforin, granzyme A, and TIA-1 by human uterine CD56+ NK cells implies they are activated and capable of effector functions.  Hum Reprod. 1993;  8 2061-2067
    PubMedGoogle Scholar
  • 20 King A, Hiby S E, Gardner L, Joseph S, Bowen J M, Verma S, Burrows T D, Loke Y W. Recognition of trophoblast HLA class I molecules by decidual NK cell receptors - a review.  Placenta. 2000;  21 (Suppl A) S81-S85
    CrossrefPubMedGoogle Scholar
  • 21 Kovats S, Main E K, Librach C, Stubblebine M, Fisher S J, DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts.  Science. 1990;  248 220-223
    CrossrefPubMedGoogle Scholar
  • 22 Lala P K, Graham C H. Mechanisms of trophoblast invasiveness and their control: The role of proteases and protease inhibitors.  Cancer Metast Rev. 1990;  9 369-379
    CrossrefPubMedGoogle Scholar
  • 23 Lin H, Mosmann T R, Guilbert L, Tuntipopipat S, Wegmann T G. Synthesis of T helper 2-type cytokines at maternal-fetal interface.  J Immunol. 1993;  151 4562-4573
    PubMedGoogle Scholar
  • 24 Marzusch K, Buchholz F, Ruck P, Handgretinger R, Geiselhart A, Engelmann L, Dietl J. Interleukin-12- and interleukin-2-stimulated release of interferon-g by uterine CD56++ large granular lymphocytes is amplified by decidual macrophages.  Human Reproduction. 1997;  12 921-924
    CrossrefPubMedGoogle Scholar
  • 25 Miki A, Ishikawa Y, Yabe T, Furukawa H, Fujii T, Tokunaga K, Akaza T, Tadokoro K, Taketani Y, Juji T. Human lymphocytes obtained from decidual tissue express killer activatory receptors as well as killer inhibitory receptors: analysis using a single strand conformation polymorphism method.  Am J Reprod Immunol. 1998;  39 271-278
    PubMedGoogle Scholar
  • 26 Miyajima A, Kitamura T, Harada N, Yokota T, Arai K. Cytokine receptors and signal transduction.  Annu Rev Immunol. 1992;  10 295-331
    CrossrefPubMedGoogle Scholar
  • 27 Mosmann T R, Coffman R L. Th1 and Th2 cells: Different patterns of lymphokine secretion lead to different functional properties.  Annu Rev Immunol. 1989;  7 145-173
    CrossrefPubMedGoogle Scholar
  • 28 Munn D H, Zhou M, Attwood J T, Bondarev I, Conway S J, Marshall B, Brown C, Mellor A L. Prevention of allogeneic fetal rejection by tryptophan catabolism.  Science. 1998;  281 1191-1193
    CrossrefPubMedGoogle Scholar
  • 29 Nishizawa K, Koyasu S. IL-2 and IL-7 differentially induce CD4-CD8-αβTCR+NK1.1+ large granular lymphocytes and IL-4-producing cells from CD4-CD8-αβTCR+NK1.1- cells: implications for the regulation of Th1- and Th2-type responses.  Int Immunol. 1997;  9 1123-1129
    CrossrefPubMedGoogle Scholar
  • 30 Pan L, Delmonte J, Jalonen C K, Ferrara J L. Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease.  Blood. 1995;  86 4422-4429
    PubMedGoogle Scholar
  • 31 Piccinni M P, Guidizi M G, Biagiotti R, Beloni L, Giannarini L, Sampognaro S, Parronchi P, Manetti R, Annunziato F, Livi C, Romagnani S, Maggi E. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones.  J Immunol. 1995;  155 128-133
    PubMedGoogle Scholar
  • 32 Piccinni M P, Romagnani S. Regulation of fetal allograft survival by hormone-controlles Th1- and Th2-type cytokines.  Immunol Res. 1996;  15 141-150
    PubMedGoogle Scholar
  • 33 Rook G A, Hernandez-Pando R, Lightman S L. Hormones, peripherally activated prohormones and regulation of the Th1/Th2 balance.  Immunol Today. 1994;  15 301-303
    CrossrefPubMedGoogle Scholar
  • 34 Rukavina D, Podack E R. Abundant perforin expression at the maternal-fetal interface: guarding the semiallogeneic transplant.  Immunol Today. 2000;  21 160-163
    CrossrefPubMedGoogle Scholar
  • 35 Sacks G, Sargent I, Redman C. An innate view of human pregnancy.  Immunol Today. 1999;  20 114-118
    CrossrefPubMedGoogle Scholar
  • 36 Saito S, Tsukaguchi N, Hasegawa T, Michimata T, Tsuda H, Narita N. Distribution of Th1, Th2 and Th0 and the Th1/Th2 cell ratios in human peripheral and endometrial T cells.  Am J Reprod Immunol. 1999;  42 240-245
    PubMedGoogle Scholar
  • 37 Sawai K, Matsuzaki N, Kameda T, Hashimoto K, Okada T, Shimoya K, Nobunaga T, Taga T, Kishimoto T, Saji F. Leukemia inhibitory factor produced at the fetomaternal interface stimulates chorionic gonadotropin production: its possible implication during pregnancy, including implantation period.  J Clin Endocrinol Metab. 1995;  80 1449-1456
    CrossrefPubMedGoogle Scholar
  • 38 Schütt C. Mütterliche antipaternale Reaktivität - auf das WIE kommt es an.  Zentralbl Gynäkol. 1999;  121 202-205
    PubMedGoogle Scholar
  • 39 Simon C, Frances A, Pellicer A, Polan M L. Cytokines in implantation.  Semin Reprod Endocrinol. 1995;  13 142-151
    PubMedGoogle Scholar
  • 40 Stallmach T, Ehrenstein T, Isenmann S, Müller C, Hengartner H, Kagi D. The role of perforin-expression by granular metrial gland cells in pregnancy.  Eur J Immunol. 1995;  25 3342-3348
    PubMedGoogle Scholar
  • 41 Stallmach T, Hebisch G, Joller-Jemelka H I, Orban P, Schwaller J, Engelmann M. Cytokine production and topographic data on cytokines during intrauterine disease.  Lab Invest. 1995;  73 384-392
    PubMedGoogle Scholar
  • 42 Stewart C L, Kaspar P, Brunet L J, Bhatt H, Gadi I, Kontgen F, Abbondanzo S J. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.  Nature. 1992;  359 76-79
    CrossrefPubMedGoogle Scholar
  • 43 Strbo N. Regulation of cytolytic activity of decidual lymphocytes: Role of cytokines IL-2 and IL-15.  Placenta. 1999;  20 A64
    PubMedGoogle Scholar
  • 44 Suthanthiran M, Strom T B. Immunobiology and immunopharmacology of organ allograft rejection.  J Clin Immunol. 1995;  15 161-171
    CrossrefPubMedGoogle Scholar
  • 45 Szereday L, Varga P, Szekeres-Bartho J. Cytokine production by lymphocytes in pregnancy.  Am J Reprod Immunol. 1997;  38 418-422
    CrossrefPubMedGoogle Scholar
  • 46 Uehara Y, Minowa O, Mori C, Shiota K, Kuno J, Noda T, Kitamura N. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor.  Nature. 1995;  373 702-705
    CrossrefPubMedGoogle Scholar
  • 47 Umekage H, Saito S, Morikawa H. Enhancement by stem cell factor of interleukin-2 (IL-2) - induced DNA synthesis in human decidual DC16-CD56bright natural killer cells mediated by increased expression of the IL-2 receptor α chain.  J Reprod Immunol. 1998;  40 1-24
    PubMedGoogle Scholar
  • 48 Vassiliadis S, Tsoukatos D, Athanassakis I. Interferon-induced class II expression at the spongiotrophoblastic zone of the murine placenta is linked to fetal rejection and developmental abnormalities.  Acta Physiol Scand. 1994;  151 485-495
    PubMedGoogle Scholar
  • 49 Wegmann T G, Lin H, Guilbert L, Mosmann T R. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a Th2 phenomenon.  Immunol Today. 1993;  14 353-356
    CrossrefPubMedGoogle Scholar

Dr. Karin Geis

Frauenklinik der Julius-Maximilians-Universität Würzburg

Josef-Schneider-Str. 4

D-97080 Würzburg

Phone: 09 31-2 01-52 51

Fax: 09 31-2 01-34 06

Email: karin.geis@gmx.de

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