Article

Diabetologia

, Volume 50, Issue 10, pp 2147-2155

Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice

  • L.-Y. KhilAffiliated withDepartment of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary
  • , H.-S. JunAffiliated withDepartment of Microbiology and Infectious Diseases, Faculty of Medicine, University of CalgaryRosalind Franklin Comprehensive Diabetes Center, Chicago Medical School Email author 
  • , H. KwonAffiliated withDepartment of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary
  • , J. K. YooAffiliated withDepartment of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary
  • , S. KimAffiliated withDepartment of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary
  • , A. L. NotkinsAffiliated withExperimental Medicine Section, Oral Infection and Immunity Branch, NIDCR, NIH
  • , J.-W. YoonAffiliated withDepartment of Microbiology and Infectious Diseases, Faculty of Medicine, University of CalgaryRosalind Franklin Comprehensive Diabetes Center, Chicago Medical School

Abstract

Aims/hypothesis

Expression of T helper (Th)1 cytokine mRNA in pregnant women is known to be inversely correlated with serum human chorionic gonadotropin (hCG). Type 1 diabetes is a Th1-mediated autoimmune disease, in which intervention at an early stage of the autoimmune process can prevent disease progression. We hypothesised that immune modulation by treating young NOD mice with hCG may prevent diabetes.

Methods

Female NOD mice were treated with hCG or recombinant hCG from 3 to 15 weeks of age and the incidence of diabetes and development of insulitis was determined. CD4+ and CD8+ T cell populations, T cell proliferation, cytokine production and CD4+CD25+ regulatory T cells were examined and adoptive transfer experiments were performed.

Results

Both purified and recombinant hCG prevented development of diabetes in NOD mice. hCG decreased the proportion and number of CD4+ and CD8+ T cells and inhibited T cell proliferative responses against beta cell antigens. hCG treatment suppressed IFN-γ production, but increased IL-10 and TGF-β production in splenocytes stimulated with anti-CD3 antibody. hCG treatment also suppressed TNF-α production in splenocytes stimulated with lipopolysaccharide. Furthermore, hCG treatment increased the CD4+CD25+/CD4+ T cell ratio in spleen and pancreatic lymph nodes. Depletion of CD4+CD25+ T cells from splenocytes of hCG-treated NOD mice abolished their preventive effect on diabetes transfer.

Conclusions/interpretation

We conclude that hCG has an immunomodulatory effect by downregulating effector cells, including Th1 cells, CD8+ T cells and macrophages, and increasing the CD4+CD25+/CD4+ T cell ratio, thus preventing autoimmune diabetes in NOD mice.

Keywords

Autoimmune disease Cytokines Human chorionic gonadotropin Immune regulation Insulitis NOD mice Regulatory T cells T cells Th1 immune response Type 1 diabetes