Transient upregulation of IDO in dendritic cells by human chorionic gonadotropin downregulates autoimmune diabetes

Objective: Pregnancy induces a state of immunological tolerance that aims at suppressing immune responses against the fetus and has been linked to temporal remission of pre-existing autoimmune disorders. To understand the mechanisms of this reversible immune regulation, we investigate the role of a key pregnancy hormone, human chorionic gonadotropin (hCG), in immune tolerance against autoimmune type 1 diabetes in nonobese diabetic (NOD) mice. Research Design and methods: We injected hCG into cytokine gene deficient NOD mice, and evaluated the effects of hCG administration on T cells and dendritic cells (DCs). Results and conclusions: We show that administration of hCG to NOD mice inhibits both the activation of diabetogenic CD4 and CD8 T cells, in vitro and in vivo, and the progression of T1D by upregulating the expression of indoleamine 2,3-dioxygenase (IDO) in dendritic cells (DCs). IDO upregulation is transient and declined shortly after hCG withdrawal. DC-depletion restores the diabetetogenic activity of splenic T cells from hCG-treated mice, and inhibition of IDO activity by 1-methyl-tryptophan (1-MT) abrogates the hCG-induced T cell suppression and resistance to T1D. We propose that hCG-induced upregulation of IDO in DCs plays a major role in pregnancy-associated resistance to autoimmunity.