Immunological mechanisms associated with long‐term remission of human type 1 diabetes

B Karges, I Durinovic‐Belló, E Heinze… - Diabetes/metabolism …, 2006 - Wiley Online Library
B Karges, I Durinovic‐Belló, E Heinze, KM Debatin, B Boehm, W Karges
Diabetes/metabolism research and reviews, 2006Wiley Online Library
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 …
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‐γ 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. Copyright © 2005 John Wiley & Sons, Ltd.
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