Dendritic Cell Stimulation by IFN-β Alters T Cell Function via Modulation of Cytokine Secretion in Diabetes Type 1

  • Saeid Abediankenari Department of Microbiology and Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • Maryam Ghasemi Mail Department of Pathology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • Mohammad Bagher Eslami Department of Pathobiology, School of Health, Tehran University of Medical Sciences, Tehran, Iran.
Cytokine, HLA-G, IFN-β (Interferon β), diabetes type 1, autoimmunity, dendritic cell


During antigen capture and processing, mature dendritic cells (DC) express large amounts of peptide-MHC complexes and accessory molecules on their surface. We investigated the role of IFN-β in induction HLA-G expression on the monocyte derived DC and cytokine profile in diabetes type 1. We accomplished secretary pattern and total cytokine production of the Th1 cytokine (IL-2, γIFN) and Th2 cytokines (IL-4, IL-10) before and after mixed leukocyte reaction (MLR) of 30 diabetic patients and 30 normal subjects.   In this study a significant increase of IL-10 and γIFN reduction after IFN-β Therapy in culture in presence of HLA-G bearing DC as compared to control were seen. It is seen that dendritic cell causes IL-10 production of T cell in vitro that reduce T cell activation from diabetes patients and normal subjects resulted to the production and expression of HLA-G on these cells from both groups. Using mixed leukocyte reaction, it was found that IFN-β-treated dendritic cell mediated the inhibition of autologous T cell activation via IL-10 production and level of HLA-G on dendritic cell may be correlated to disease activity in diabetes patients and it could also serve as a useful marker for disease progress and treatment.


Berman MA, Sandborg CI, Wang Z, Imfeld KL, Zaldivar F Jr, Dadufalza V, et al. Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. J Immunol 1996;157(10):4690-6.

Rabinovitch A, Suarez-Pinzon WL. Roles of cytokines in the pathogenesis and therapy of type 1 diabetes. Cell Biochem Biophys 2007;48(2-3):159-63.

Suarez-Pinzon WL, Rabinovitch A. Combination therapy with epidermal growth factor and gastrin delays autoimmune diabetes recurrence in nonobese diabetic mice transplanted with syngeneic islets. Transplant Proc 2008;40(2):529-32.

Kallmann BA, Lampeter EF, Hanifi-Moghaddam P, Hawa M, Leslie RD, Kolb H. Cytokine secretion patterns in twins discordant for Type I diabetes. Diabetologia 1999;42(9): 1080-5.

Liu D, Cardozo AK, Darville MI, Eizirik DL. Doublestranded RNA cooperates with interferon-gamma and IL-1 beta to induce both chemokine expression and nuclear factor- kappa B-dependent apoptosis in pancreatic beta-cells: potential mechanisms for viral-induced insulitis and betacell death in type 1 diabetes mellitus. Endocrinology 2002;143(4):1225-34.

Radu DL. Cellular mechanisms involved in experimental insulin-dependent diabetes mellitus. Roum Arch Microbiol Immunol 2001;60(3):203-26.

Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation? Diabetes 1994;43(5):613-21.

Castano L, Eisenbarth GS. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol 1990;8:647-79.

Azam A, Eisenbarth GS. Immunopathogenesis and immunotherapeutic approaches to type 1A diabetes. Expert Opin Biol Ther 2004;4(10):1569-75.

Roep BO. The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cure. Diabetologia 2003;46(3):305-21.

Wilson DB. Immunology: Insulin auto-antigenicity in type 1 diabetes. Nature 2005;438(7067):E5.

Biron CA. Interferons alpha and beta as immune regulators: a new look. Immunity 2001;14(6):661-4.

Karp CL, Biron CA, Irani DN. Interferon beta in multiple sclerosis: is IL-12 suppression the key? Immunol Today 2000;21(1):24-8.

Jun HS, Yoon JW. The role of viruses in type I diabetes: two distinct cellular and molecular pathogenic mechanisms of virus-induced diabetes in animals. Diabetologia 2001;44(3):271-85.

Le Rond S, Le Maoult J, Créput C, Menier C, Deschamps M, Le Friec G, et al. Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients. Eur J Immunol 2004;34(3):649-60.

Solier C, Aguerre-Girr M, Lenfant F, Campan A, Berrebi A, Rebmann V, et al. Secretion of pro-apoptotic intron 4- retaining soluble HLA-G1 by human villous trophoblast. Eur J Immunol 2002;32(12):3576-86.

Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 2008;26(1):212-22.

Bukur J, Rebmann V, Grosse-Wilde H, Luboldt H, Ruebben H, Drexler I, et al. Functional role of human leukocyte antigen-G up-regulation in renal cell carcinoma. CancerRes 2003;63(14):4107-11.

Créput C, Durrbach A, Menier C, Guettier C, Samuel D,Dausset J, et al. Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation. J Hepatol 2003;39(4):587-94.

Fainardi E, Rizzo R, Melchiorri L, Vaghi L, Castellazzi M, Marzola A, et al. Presence of detectable levels of soluble HLA-G molecules in CSF of relapsing-remitting multiple sclerosis: relationship with CSF soluble HLA-I and IL-10 concentrations and MRI findings. J Neuroimmunol 2003;142(1-2):149-58.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65(1-2):55-63.

Severa M, Remoli ME, Giacomini E, Ragimbeau J, Lande R, Uzé G, et al. Differential responsiveness to IFN-alpha and IFN-beta of human mature DC through modulation of IFNAR expression. J Leukoc Biol 2006;79(6):1286-94.

Bastürk B, Karakayali F, Emiroğlu R, Sözer O, Haberal A, Bal D, et al. Human leukocyte antigen-G, a new parameter in the follow-up of liver transplantation. Transplant Proc 2006;38(2):571-4.

Takeuchi S, Furue M. Dendritic cells: ontogeny. Allergol Int 2007;56(3):215-23.

Reder AT, Genç K, Byskosh PV, Porrini AM. Monocyte activation in multiple sclerosis. Mult Scler 1998;4(3):162-8.

Wiendl H, Mitsdoerffer M, Hofmeister V, Wischhusen J, Bornemann A, Meyermann R, et al. A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. J Immunol 2002;168(9):4772-80.

Lila N, Rouas-Freiss N, Dausset J, Carpentier A, Carosella ED. Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism. Proc Natl Acad Sci U S A 2001;98(21):12150-5.

Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, et al. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol 2002;3(3):237-43.

Colonna M, Samaridis J, Cella M, Angman L, Allen RL, O'Callaghan CA, et al. Human myelomonocytic cells expressan inhibitory receptor for classical and nonclassical MHC class I molecules. J Immunol 1998;160(7):3096-100.

Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB J 2005;19(7):681-93.

Falcone M, Yeung B, Tucker L, Rodriguez E, Krahl T, Sarvetnick N. IL-4 triggers autoimmune diabetes by increasing self-antigen presentation within the pancreatic Islets. Clin Immunol 2001;98(2):190-9.

Buelens C, Willems F, Delvaux A, Piérard G, Delville JP,Velu T, et al. Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on human peripheral blood dendritic cells. Eur J Immunol 1995;25(9):2668-72.

Wilson SB, Kent SC, Patton KT, Orban T, Jackson RA, Exley M, et al. Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes. Nature 1998;391(6663):177-81.

How to Cite
Abediankenari S, Ghasemi M, Eslami MB. Dendritic Cell Stimulation by IFN-β Alters T Cell Function via Modulation of Cytokine Secretion in Diabetes Type 1. Acta Med Iran. 47(5):341-347.