Amir Hassan Zarnani
1- Immunology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran, Iran
2- Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
Seyyed Mohammad Moazzeni Corresponding Author
- Immunology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran, Iran
Fazel Shokri
- Immunology Department, Faculty of Medical Science, Tehran University of Medical Science, Tehran, Iran
Mojdeh Salehnia
- Anatomy Department, Faculty of Medical Sciences, Tarbiyat Modares University, Tehran, Iran
Mahmood Jeddi-Tehrani
1- Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran
2- Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

Received: 4/1/2004 Accepted: 4/1/2004 - Publisher : Avicenna Research Institute

Related Articles


Other Format



Introduction: Despite the unrecognized nature of fetal antigens for maternal immune system, the fetus is usually not rejected and is rather sustained by maternal immune system. The immunological mechanisms that protect the fetus from rejection are not completely understood. One of the main hypotheses is the appearance of immuno-suppressive factors in the feto-maternal interface that suppress maternal immune responses against the fetus. Although the effects of decidual or placental cell culture supernatants on the function of different immune cells have been studied, the effects of such factors on dendritic cells (DCs) have not been evaluated yet. In this study the immunomodulatory activity of decidual cell culture supernatants on in vivo antigen presentation by DCs has been addressed. Materials and Methods: Decidual cells obtained from the uteri of allogenic pregnant mice (Balb/c× C57BL/6) on day 12 post conception, were cultured for 48 hours and supernatants collected. DCs were purified from Balb/c mice spleens by a four step method including collagenase digestion of splenic tissues, selection of low density cells by Optiprep density gradient centrifugation, plastic adherence and overnight culture. The purity of dendritic cells was detected by flow cytometry method using anti CDllc antibodies. During overnight cultures, DCs were pulsed with antigen. In some cultures decidual supernatants were added at 5%, 10% or 20% fractions of the final volume. Antigen pulsed DCs were injected into the footpads of syngeneic mice and after 5 days, draining lymph nodes were excised. Lymph node cells of immunized mice were cultured in the presence of antigen and the rates of cell proliferation were measured on the 4th day by thymidine incorporation. Results: The results showed that antigen-pulsed DCs primed antigen-specific lymphocytes efficiently and the primed lymphocytes did proliferate vigorously in response to recall antigen in vitro (cpm=89210 3632). Treatment of DCs with decidual culture supernatants by any concentration, markedly blocked antigen presention by these cells and significantly reduced the extent of antigen-specific proliferation of lymphocytes primed with such DCs. (cpm= 6200582) (p<0.0001 ). conclusion: to our knowledge this is the first report on the effect of decidual culture supernatants on antigen presentation by dcs. it seems that inhibition of antigen presentation by dcs is one of the main mechanisms of maternal immunological tolerance to the fetus since dcs, as the most potent antigen presenting cells, could potentially present paternal antigens to maternal t lymphocytes and thereby provoke destructive immunological responses to the fetus.< pan>

Keywords: Dendritic cell, Antigen presentation, Decidua, Cell culture supernatant, Pregnancy, Fetus

To cite this article:


  1. Bouma G.J., Van Caubergh P., Van Bree S.P., Castelli-Visser R.M., Witvliet M.D., Van der Meer-Prins E.M., Van Rood J.J., Claas F.H. Preg-nancy can induce prinming of cytotoxic T lymph-ocytes specific for paternal HLA antigens that is associated with antibody formation. Transplant-ation.1996;62(5):672-8.
  2. Billingham R.E., Brent L., Medawar P.B. Acti-vely acquired tolerance of foreign cells.1953. Transplantation.2003;76(10):1409-12.
  3. Hoskin D.W., Murgita R.A. Specific maternal anti-fetal lymphoproliferative responses and their regulation by natural immunosuppressive factors. Clin Exp Immunol.1989;76(2):262-7.
  4. Mellor A.L., Munn D.H. Immunology at the maternal-fetal interface: lessons for T cell toler-ance and suppression. Annu Rev Immunol.2000; 18:367-91(Review).
  5. Borland R. Placenta as an allograft. In. Compa-rative placentation. Eds. Steven DH. London, Academic press.1975;pp:268-281.
  6. Tafuri A., Alferink J., Moller P., Hammerling G.J., Arnold B. T cell awareness of paternal allo- antigens during pregnancy.Science.1995;270 (5236):630-3.
  7. مصفـا نـريمان، زرنانـي اميـرحسـن، حسن زهير محمـد. ايمونولوژي حاملگي طبيعي. تهران،‌ انتشارات دانشگاه علوم پزشكي و خدمات بهداشتي– درماني شهيد بهشتي، چاپ اول 1382.
  8. اميرحسن زرناني، سيد محمد مؤذني، فاضل شكري، مژده صالح‌نيا، علي‌احمد بيات، محمـود جدي تهـراني. بهينه‌سـازي تخليص سلول‌هاي دندريتيك طحال موش به منظور استفاده در تخليص و مطالعه سلول‌هاي دندريتيك ارگان‌هاي تــوليد مثـل. فصـلنامه باروري و ناباروري، سـال چهـارم (1381)، شماره 1، صفحات 29-17.
  9. Pool T. The UFAW handbook on the care & management of laboratory animals, Longman scientific & Technical, 6th Edition.1989;pp:289- 323.
  10. Inaba K., Metlay J.P., Crowley M.T., Stein-man R.M. Dendritic cells pulsed with protein anti- gens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med.1990;172(2): 631-40.
  11. Pippard D.F. In-vitro development and degen- eration of stromal cells from the uterus of the rat at three stages of pregnancy. J Reprod Fertil.1987; 81(1):249-57.
  12. Vladimirsky F., Chen L., Amsterdam A., Zor U., Lindner H.R. Differentiation of decidual cells in cultures of rat endometrium. J Reprod Fertil. 1977;49(1):61-8.
  13. Olivares E.G., Montes M.J., Oliver C., Gali-ndo J.A., Ruiz C. Cultured human decidual stro-mal cells express B7-1 (CD80) and B7-2 (CD86) and stimulate allogeneic T cells. Biol Reprod. 1997;57(3):609-15.
  14. Badet M.T., Bell S.C., Billington W.D. Immu- noregulatory activity of supernatants from short-term cultures of mouse decidual tissue. J Reprod Fertil.1983;68(2):351-8.
  15. Badet M.T., Bell S.C., Billington W.D. Partial characterization of immunosuppressive factors from short-term cultures of murine decidual tissue Ann Immunol (Paris).1983;134C(3):321 -9.
  16. Beer A.E., and Billingham R.E. Host respons-es to intra-uterine tissue, cellular and fetal allo-grafts. J Reprod Fert.1974;21:59-88.
  17. Dodd M., Andrew T.A., Coles J.S. Functional behaviour of skin allografts transplanted to rabbit deciduomata. J Anat.1980;130(2):381-90.
  18. Kolb J.P., Chaouat G., Chassoux D. Immuno-active products of placenta. III. Suppression of natural killing activity. J Immunol.1984;132(5): 2305-10.
  19. Chaouat G., Kolb J.P. Immunoactive products of placenta. IV. Impairment by placental cells and their products of CTL function at effector stage. J Immunol.1985;135(1):215-22.
  20. Le Friec G., Laupeze B., Fardel O., Sebti Y., Pangault C., Guilloux V., Beauplet A., Fauchet R., Amiot L. Soluble HLA-G inhibits human den-dritic cell-triggered allogeneic T-cell proliferation without altering dendritic differentiation and maturation processes. Hum Immunol.2003;64(8): 752-61.
  21. Liang S., Baibakov B., Horuzsko A. HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor. Eur J Immunol.2002;32(9):2418-26.
  22. Zheng Z., Narita M., Takahashi M., Liu A., Furukawa T., Toba K., Aizawa Y. Induction of T cell anergy by the treatment with IL-10-treated dendritic cells. Comp Immunol Microbiol Infect Dis.2004;27(2):93-103.
  23. Steinbrink K., Jonuleit H., Muller G., Schuler G., Knop J., Enk A.H. Interleukin-10-treated hu-man dendritic cells induce a melanoma-antigen- specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood.1999;93(5): 1634-42.
  24. Steinbrink K., Wolfl M., Jonuleit H., Knop J., Enk A.H. Induction of tolerance by IL-10-treated dendritic cells. J Immunol.1997;159(10):4772-80.
  25. Levings M.K., Sangregorio R., Roncarolo M. G. Human CD25(+)CD4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of func-tion. J Exp Med.2001;193(11):1295-302.
  26. Steinbrink K., Graulich E., Kubsch S., Knop J., Enk A.H. CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood.2002;99(7):2468-76.
  27. Anteby S.O., Bauminger S., Zor U., Lindner H.R. Prostaglandin synthesis in decidual tissue of the rate uterus. Prostaglandins.1975;10(6):991-9.
  28. Kalinski P., Schuitemaker J.H., Hilkens C.M., Kapsenberg M.L. Prostaglandin E2 induces the final maturation of IL-12-deficient CD1a+CD83+ dendritic cells: the levels of IL-12 are determined during the final dendritic cell maturation and are resistant to further modulation. J Immunol.1998; 161(6):2804-9.
  29. Penna G., Adorini L. 1 Alpha, 25-dihydroxy-vitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immu-nol.2000;164(5):2405-11.
  30. Berer A., Stockl J., Majdic O., Wagner T., Kollars M., Lechner K., Geissler K., Oehler L. 1,25-Dihydroxyvitamin D(3) inhibits dendritic cell differentiation and maturation in vitro. Exp Hematol.2000;28(5):575-83.
  31. Dong X., Bachman L.A., Kumar R., Griffin M.D. Generation of antigen-specific, interleukin-10- producing T-cells using dendritic cell stimula-tion and steroid hormone conditioning. Transpl Immunol.2003;11(3-4):323-33.
  32. Xing N. L., Maldonado M.L., Bachman L.A., McKean D.J., Kumar R., Griffin M.D. Distinctive dendritic cell modulation by vitamin D(3) and glucocorticoid pathways. Biochem Biophys Res Commun.2002;297(3):645-52.
  33. Liu H.Y., Buenafe A.C., Matejuk A., Ito A., Zamora A., Dwyer J., Vandenbark A.A., Offner H. Estrogen inhibition of EAE involves effects on dendritic cell function. J Neurosci Res.2002;70(2) : 238-48.
  34. Wira C.R., Kaushic C., Richardson J. Role of sex hormones and cytokines in regulating the mucosal immune system in the femal reproductive tract. In: Mucosal Immunology. Orga P. (Editors) Aca-demic Press.1999; pp: 1449-1461.
  35. Fata J.E., Chaudhary V., Khokha R. Cellular turnover in the mammary gland is correlated with systemic levels of progesterone and not 17beta- estradiol during the estrous cycle. Biol Reprod. 2001;65(3):680-8.
  36. Vlad G., Piazza F., Colovai A., Cortesini R., Della Pietra F., Suciu-Foca N., Manavalan J.S. Interleukin-10 induces the upregulation of the inhibitory receptor ILT4 in monocytes from HIV positive individuals. Hum Immunol.2003;64(5):
  37. Wira C.R., Roche M.A., Rossoll R.M. Anti-gen presentation by vaginal cells: role of TGFbeta as a mediator of estradiol inhibition of antigen presentation. Endocrinology.2002;143 (8):2872-9.
  38. Angeli V., Faveeuw C., Roye O., Fontaine J., Teissier E., Capron A., Wolowczuk I., Capron M., Trottein F. Role of the parasite-derived prosta- glandin D2 in the inhibition of epidermal Langer-hans cell migration during schistosomiasis infec-tion. J Exp Med.2001;193(10):1135-47.
  39. Rees M.C., Kelly R.W. Prostaglandin D2 release by endometrium and myometrium. Br J Obstet Gynaecol.1986;93(10):1078-82.


Home | About Us | Current Issue | Past Issues | Submit a Manuscript | Instructions for Authors | Subscribe | Search | Contact Us

"Journal of Reproduction & Infertility" is owned, published, and managed by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution –NonCommercial 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Journal of Reproductoin and Infertility (JRI) is a member of COMMITTEE ON PUBLICATION ETHICS . Verify here .

©2024 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.