Molecular Biology Reports

, Volume 39, Issue 6, pp 6633–6639 | Cite as

Functional study of immature dendritic cells co-transfected with IL-10 and TGF-beta 1 genes in vitro



Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previous studies suggest that immature dendritic cells (imDCs) might be involved in the induction of peripheral T cell tolerance. While interleukin-10 (IL-10) functions at different levels of the immune response, transforming growth factor-beta 1 (TGF-beta 1) is considered to be a key factor in immune tolerance. In this study, we investigated the effects of immature DC (imDC) co-transfected with IL-10 and TGF-beta 1 genes (IL-10-TGF-beta 1-imDC) on inducing immune tolerance. Moreover, we compared the effects of IL-10-TGF-beta 1-imDC with IL-10 transfected imDC (IL-10-imDC) and TGF-beta 1-transfected imDC (TGF-beta 1-imDC), respectively. IL-10-TGF-beta 1-imDC resulted in the down-regulation of MHC class II, CD80 and CD86. IL-10-TGF-beta 1-imDC could induce T cell hyporesponsiveness, and was reluctant to proliferate. IL-10-TGF-beta 1-imDC was more effective than IL-10-imDC and TGF-beta 1-imDC, respectively. In summary, co-expression of IL-10 and TGF-beta 1 affected the immunity of imDCs and enhanced their tolerogenicity. It might be a promising therapy for donor-specific tolerance after organ transplantation.


Dendritic cells Transforming growth factor-beta1 Interleukin-10 Immune tolerance 



The authors thank Mrs. Lingyun Gao for her excellent technical assistance. This study was supported by Fujian Provincial Natural Foundation (No. 2009D066) and Fujian Medical University Foundation (No. 09ZD007).


  1. 1.
    Denton MD, Magee CC, Saygh MH (1999) Immunosuppressive strategies in transplantation. Lancet 353:1083–1091PubMedCrossRefGoogle Scholar
  2. 2.
    Womer KL, Vella JP, Sayegh MH (2000) Chronic allograft dysfunction: mechanisms and new approaches to therapy. Semin Nephrol 20:126–147PubMedGoogle Scholar
  3. 3.
    Ureta G, Osorio F, Morales J et al (2007) Generation of dendritic cells with regulatory properties. Transpl Proc 39:633–637CrossRefGoogle Scholar
  4. 4.
    Griffiths KL, O’Neill HC (2008) Dendritic cells as immune regulators, the mouse model. J Cell Mol Med 12:1909–1914PubMedCrossRefGoogle Scholar
  5. 5.
    Cools N, Van Tendeloo VF, Smits EL et al (2008) Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells. J Cell Mol Med 12:690–700PubMedCrossRefGoogle Scholar
  6. 6.
    Ye Z, Huang H, Hao S et al (2007) IL-10 has a distinct immunoregulatory effect on naive and active T cell subsets. J Interferon Cytokine Res 27:1031–1038PubMedCrossRefGoogle Scholar
  7. 7.
    Mocellin S, Panelli MC, Wang E et al (2003) The dual role of IL-10. Trends Immunol 24:36–43PubMedCrossRefGoogle Scholar
  8. 8.
    Yang L, Pang Y, Moses HL (2010) TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol 31:220–227PubMedCrossRefGoogle Scholar
  9. 9.
    Nasef A, Chapel A, Mazurier C et al (2007) Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells. Gene Expr 13:217–226PubMedCrossRefGoogle Scholar
  10. 10.
    Liu N, Duan TD, Zheng N (2006) Effects of TGF-beta1, gene modified donor dendritic cells on immune repulsion. J Sichuan Univ (Med Sci Edi) 37:721–725Google Scholar
  11. 11.
    Cai Z, Zhang W, Li M et al (2010) TGF-beta1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4(+)Foxp3(+) regulatory T cells. Cell Mol Immunol 7:35–43PubMedCrossRefGoogle Scholar
  12. 12.
    Spender LC, O’Brien DI, Simpson D et al (2009) TGF-beta induces apoptosis in human B cells by transcriptional regulation of BIK and BCL-XL. Cell Death Differ 16:593–602PubMedCrossRefGoogle Scholar
  13. 13.
    Kel JM, Girard-Madoux MJ, Reizis B et al (2010) TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis. J Immunol 185:3248–3255PubMedCrossRefGoogle Scholar
  14. 14.
    Govinden R, Bhoola KD (2003) Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther 98:257–265PubMedCrossRefGoogle Scholar
  15. 15.
    Mantel PY, Schmidt-Weber CB (2011) Transforming growth factor-beta: recent advances on its role in immune tolerance. Methods Mol Biol 677:303–338PubMedCrossRefGoogle Scholar
  16. 16.
    Abediankenari S, Ghasemi M (2009) Generation of immune inhibitory dendritic cells and CD4+ T regulatory cells inducing by TGF-beta. Iran J Allergy Asthma Immunol 8:25–30PubMedGoogle Scholar
  17. 17.
    Panther E, Idzko M, Corinti S et al (2002) The influence of lysophosphatidic acid on the functions of human dendritic cells. J Immunol 169:4129–4135PubMedGoogle Scholar
  18. 18.
    Abe K, Yarovinsky FO, Murakami T et al (2003) Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo. Blood 101:1477–1483PubMedCrossRefGoogle Scholar
  19. 19.
    Biragyn A, Rufini PA, Leifer CA et al (2002) Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298:1025–1029PubMedCrossRefGoogle Scholar
  20. 20.
    Zhou X, Yang N, Lu L et al (2007) Up-regulation of IL-10 expression in dendritic cells is involved in Trichosanthin induced immunosuppression. Immunol Lett 110:74–81PubMedCrossRefGoogle Scholar
  21. 21.
    Li X, Dou KF, Liu HL et al (2007) Immune tolerance induced by IL-10 and methylprednisolone modified dendritic cells in vitro. Chin J Cell Mol Immunol 23:436–438Google Scholar
  22. 22.
    Xiao BG, Zhu WH, Lu CZ (2007) The presence of GM-CSF and IL-4 interferes with effect of TGF-beta1 on antigen presenting cells in patients with multiple sclerosis and in rats with experimental autoimmune encephalomyelitis. Cell Immunol 249:30–36PubMedCrossRefGoogle Scholar
  23. 23.
    Yang DH, Park JS, Jin CJ et al (2009) The dysfunction and abnormal signaling pathway of dendritic cells loaded by tumor antigen can be overcome by neutralizing VEGF in multiple myeloma. Leuk Res 33:665–670PubMedCrossRefGoogle Scholar
  24. 24.
    Li WM, Liu W, Gao C et al (2006) Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats. Chin Med J 119:1646–1652PubMedGoogle Scholar
  25. 25.
    Hua N, Yamashita K, Hashimoto T et al (2004) Gene therapy-mediated CD40L and CD28 co-stimulatory signaling blockade plus transient anti-xenograft antibody suppression induces long-term acceptance of cardiac xenografts. Transplantation 78:1463–1470PubMedCrossRefGoogle Scholar
  26. 26.
    Lee WC, Zhong C, Qian S et al (1998) Phenotype, function, and in vivo migration and survival of allogeneic dendritic cell progenitors genetically engineered to express TGF-beta. Transplantation 66:1810–1817PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Department of PathologyFujian Medical UniversityFuzhouChina
  2. 2.Division of Thoracic SurgeryThe First Affiliated Hospital of Fujian Medical UniversityFuzhouChina
  3. 3.Shengli Clinical Medical CollegeFujian Medical UniversityFuzhouChina
  4. 4.Divison of Hepatobiliary Surgery, Hepatic Disease CenterThe First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Personalised recommendations