HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tiittanen, M. Articles by Vaarala, O. Search for Related Content PubMed PubMed Citation Articles by Tiittanen, M. Articles by Vaarala, O. Social Bookmarking                What's this?

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

¹ Department of Viral Diseases and Immunology, Laboratory for Immunology, National Public Health Institute, Helsinki, Finland
² Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
³ Department of Pediatrics, Tampere University Hospital, Tampere, Finland
⁴ Department of Molecular and Clinical Medicine, Linköping University, Linköping, Sweden

Address correspondence and reprint requests to Minna Tiittanen, National Public Health Institute, Department of Viral Diseases and Immunology, Laboratory for Immunology, Mannerheimintie 166, 00300 Helsinki, Finland. E-mail: minna.tiittanen{at}ktl.fi

Abbreviations: CTLA-4, cytotoxic T-lymphocyte antigen-4; ICOS, inducible co-stimulator; IAA, insulin autoantibody; IFN-, -interferon; IL, interleukin; PBMC, peripheral blood mononuclear cell; TGF, transforming growth factor; Th, T-helper

Patients with type 1 diabetes are treated with daily injections of human insulin, an autoantigen expressed in thymus. Natural CD4+CD25^high 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-ß, Foxp3, cytotoxic T-lymphocyte antigen-4 [CTLA-4], and inducible co-stimulator [ICOS]) or cytokines (-interferon [IFN-], interleukin [IL]-5, IL-4) was measured by quantitative RT-PCR. The secretion of IFN-, 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. E. Fineberg, T. T. Kawabata, D. Finco-Kent, R. J. Fountaine, G. L. Finch, and A. S. Krasner Immunological Responses to Exogenous Insulin Endocr. Rev., October 1, 2007; 28(6): 625 - 652. [Abstract] [Full Text] [PDF]