Immunological Mechanisms Associated With Long-term Remission Of Human Type 1 Diabetes

Abstract

BACKGROUND: Preservation of beta cell function is a central goal in type 1 diabetes (type 1 DM) immune intervention. The characterization of individuals with recovery from established type 1 DM should provide insight into regulatory mechanisms of beta cell autoimmunity. METHODS: We studied a patient with antibody-positive type 1 DM with complete recovery of beta cell function for an observation period of 60 months. Using a preproinsulin (PPI) peptide library approach and in vitro cytokine profiling, cellular autoimmunity was characterized in peripheral blood mononuclear cells (PBMC) and CD4(+) T-helper cell subsets. RESULTS: A predominant secretion of interleukin-10 (IL-10) was detected in the patient's PBMC, mostly attributable to naïve and recently primed CD45(+)RA(+) T cells, with limited PPI epitope recognition. In contrast to a cohort of patients with permanent type 1 DM, interferon-gamma secretion was low in PBMC and CD45(+)RA(+), but not in CD45(+)RA(-) insulin-reactive T lymphocytes. Autoantibodies against islet cells, tyrosine phosphatase IA-2, GAD65 and insulin were positive at diabetes onset, but gradually declined during follow-up. CONCLUSIONS: Our observations support the concept that IL-10-dependent regulatory CD4(+) T-cell pathways are involved in beta cell recovery after the onset of hyperglycemia in autoimmune type 1 DM.