Insulin treatment in patients with type 1 diabetes induces upregulation of regulatory T-cell markers in peripheral blood mononuclear cells stimulated with insulin in vitro
2006 (English)In: Diabetes, ISSN 0012-1797, Vol. 55, no 12, 3446-3454 p.Article in journal (Refereed) Published
Patients with type 1 diabetes are treated with daily injections of human insulin, an autoantigen expressed in thymus. Natural CD4+CD25high regulatory T-cells are derived from thymus, and accordingly human insulin-specific regulatory T-cells should exist. We had a chance to study peripheral blood mononuclear cells (PBMCs) from children with type 1 diabetes both before and after starting insulin treatment, and thus we could analyze the effects of insulin treatment on regulatory T-cells in children with type 1 diabetes. PBMCs were stimulated for 72 h with bovine/human insulin. The mRNA expression of regulatory T-cell markers (transforming growth factor-β, Foxp3, cytotoxic T-lymphocyte antigen-4 [CTLA-4], and inducible co-stimulator [ICOS]) or cytokines (γ-interferon [IFN-γ], interleukin [IL]-5, IL-4) was measured by quantitative RT-PCR. The secretion of IFN-γ, IL-2, IL-4, IL-5, and IL-10 was also studied. The expression of Foxp3, CTLA-4, and ICOS mRNAs in PBMCs stimulated with bovine or human insulin was higher in patients on insulin treatment than in patients studied before starting insulin treatment. The insulin-induced Foxp3 protein expression in CD4+CD25 high cells was detectable in flow cytometry. No differences were seen in cytokine activation between the patient groups. Insulin stimulation in vitro induced increased expression of regulatory T-cell markers, Foxp3, CTLA-4, and ICOS only in patients treated with insulin, suggesting that treatment with human insulin activates insulin-specific regulatory T-cells in children with newly diagnosed type 1 diabetes. This effect of the exogenous autoantigen could explain the difficulties to detect in vitro T-cell proliferation responses to insulin in newly diagnosed patients. Furthermore, autoantigen treatment-induced activation of regulatory T-cells may contribute to the clinical remission of the disease. © 2006 by the American Diabetes Association.
Place, publisher, year, edition, pages
2006. Vol. 55, no 12, 3446-3454 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-36123DOI: 10.2337/db06-0132Local ID: 30001OAI: oai:DiVA.org:liu-36123DiVA: diva2:256971