Volume 7, Issue 3, Number 28 / October-December 2006
(pages 187-197)

Effect of pregnant mouse serum on induction of indolamine 2, 3- dioxygenase in dendritic cells

Shoreh Nikoo
Immunology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran, Iran

Seyyed Mohammad Moazzeni Corresponding Author
Immunology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran, Iran

Mahmood Bozorgmehr
Immunology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran, Iran

Amir Hassan Zarnani
1- Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
2- Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

Received: 10/1/2006 Accepted: 10/1/2006
Publisher : Avicenna Research Institute

Related Articles


Other Format


Introduction: Several studies have shown that many factors are involved in the maternal tolerance to the fetus. Indolamine 2, 3- dioxygenase (IDO) enzyme which catabolizes tryptophan is one of the factors that have been reported to play an important role leading to a successful pregnancy. The objective of this study was to evaluate the effects of pregnant mouse serum on the induction of indolamine 2, 3 dioxygenase in dendritic cells (DCs) which may be used as a basis for practical studies on the immunological bases of recurrent abortions. Materials & Methods: Allogenic pregnant mice sera were collected in mid-pregnancy. DCs were isolated from Balb/c mouse spleen through a three-step method, including: Collagenase digestion of spleen tissue, low density cells separation via the Nycodenz density gradient centri-fugation and plastic adherence. T cells were isolated from C57BL/6 mouse lymph nodes through nylon wool method. As stimulator cells, pregnant and non-pregnant mice sera treated DCs were irradiated and co-cultured with purified T cells (allogenic MLR). 1-methyl-tryptophan (1-MT), as the specific inhibitor of IDO, was added to some wells of MLR assay in different concentrations and T cells proliferation response was measured by 3H-Thymidine incorporation. The MLR supernatant was also analyzed by HPLC for its tryptophan and kynurenin (Trp metabolite) content. All tests were repeated for 5 times. Man-Whitneys non- parametric test was used to evaluate the differences among groups. Confidence interval was 95% and p-values<0.05 were regarded as significantresults: the results showed the ability of pregnant mice sera to reduce the dendritic cells ability in t cell proliferation induction compared to non-pregnant mice sera but addition of 1-mt did not have any significant effect on this inhibition. additionally, ido metabolites concentration assessment in the presence or absence of 1-mt, through hplc method, did not show any significant difference.conclusion: there are many factors in pregnant mice sera such as progesterone, il-10, vit d3, etc. which might cause inhibition of t lymphocyte proliferation response in allogenic mlr through affecting dcs efficiency. although it seems that ido expression by dcs is not respon-sible for decrease in t cell proliferation after treatment of dcs by pregnant mice sera, thus some other mechanisms might be responsible for this phenomenon which their identification needs more investigation.< pan>

Keywords: Pregnancy, Dendritic cell, IDO, Allogenic MLR, HPLC, Indolamine 2,3- dioxygenase

To cite this article:

  1. Heybon K, Silver R. Immunology of postimplantation. In Reproductive immunology. Black Well Science 1996; Chapters 14 & 15
  2. Bhzrdwaj N. The modulation of immunity by dendritic cells. Clin. Applied Immunol. Rev 2003; 3: 173-182
  3. Mellor AL, Munn DH. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 1999;20(10):469-73.
  4. Mellor AL, Sivakumar J, Chandler P, Smith K, Molina H, Mao D. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2001; 2(1): 64-8
  5. Shojaeian J, Moazzeni SM, Zarnani AH. [Investigation on effects of pregnant mouse serum on dendritic cell Function using allogeneic MLR model]. J Reprod Infertil. 2004;5(3):200-7. Persian.   [Abstract]
  6. Zarnani A.H., Moazzeni S.M., Shokri F., Salehnia M., Dokouhaki P., Shojaeian J., Jeddi-Tehrani M. The efficient isolation of murine splenic dendritic cells and their cytochemical features. Histochem Cell Biol.2006;126 (2): 275-82   [PubMed]
  7. Munn D. Ligation of B7-1/B7-2 by human CD4+ T cells triggers Indoleamine 2,3- dioxygenase activity in dendritic cells. J Immunol 2004;172:4100-4110   [PubMed]
  8. Luppi P. How immune mechanisms are affected by pregnancy. Vaccine 2003;21:3352-3357   [PubMed]
  9. Terness P, Bauer TM, Rose L, Dufter C, Watzlik A, Simon H. Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med 2002; 196(4): 447-57   [PubMed]
  10. Thellin O, Heinen E. Pregnancy and the immune system: between tolerance and rejection. Toxicol 2003;185:179-184   [PubMed]
  11. Manak RC. Mitogenic responses of peripheral blood lymphocytes from pregnant and ovariectomized heifers and their modulation by serum. J Reprod Immunol 1982; 4: 263-276   [PubMed]
  12. Penna G, Adorini L. 1 Alpha, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired allureactive T cell activation. J Immunol. 2000;164(5):2405-11   [PubMed]
  13. Huck B, Steck T, Habersack M, Dietl J, Kammerer U. Pregnancy associated hormones modulate the cytokine production but not the phenotype of PBMC-derived human dendritic cell. Eur J Obstet Gynecol Reprod Biol. 2005;1:122   [PubMed]
  14. Liang J, Sun L. Progesterone regulates mouse dendritic cells differentiation and maturation. Int Immunopharmacol. 2006;6:830-838   [PubMed]
  15. Polanczyk MJ, offner C. Estrogen-mediated immuno-modulation involves reduced activation of effector T cells, potentiation of Treg cells, and enhanced expre-ssion of the PD-1 costimulatory pathway. J Neurosci Res. 2006.   [PubMed]
  16. Tatsumi K, Higuchi T, Fujiwara H, Nakayama T, Egawa H, Itoh K, et al. Induction of tryptophan 2, 3-dioxygenase in the mouse endometrium during implan-tation. Biochem Biophys Res Commun 2000;274(1): 166-70.   [PubMed]
  17. Kudo Y, Boyd CA. Human placental indoleamine 2, 3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection. Biochim Biophys Acta. 2000;1500(1):119-24   [PubMed]
  18. Mellor AL, Sivakumar J, Chandler P, Smith K, Molina H, Mao D. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol. 2001;2(1):64-8   [PubMed]

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 copyrighted by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported 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 .

©2020 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.