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

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.