Immunological mechanisms associated with long-term remission of human type 1 diabetes.
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.
Karges
Beate
B
University Children's Hospital, University of Ulm, Ulm, Germany.
Durinovic-Belló
Ivana
I
Heinze
Eberhard
E
Debatin
Klaus-Michael
KM
Boehm
Bernhard
B
Karges
Wolfram
W
D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D012075:Remission, Spontaneous; D013997:Time Factors
D016753:Interleukin-10