Details

Autor(en) / Beteiligte

• BRUSKO, Todd
• WASSERFALL, Clive
• ATKINSON, Mark
• MCGRAIL, Kieran
• SCHATZ, Richard
• LEE VIENER, Hilla
• SCHATZ, Desmond
• HALLER, Michael
• ROCKELL, Jennifer
• GOTTLIEB, Peter
• CLARE-SALZLER, Michael

Titel

No Alterations in the Frequency of FOXP3+ Regulatory T-Cells in Type 1 Diabetes

Ist Teil von

• Diabetes (New York, N.Y.), 2007-03, Vol.56 (3), p.604-612

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• No Alterations in the Frequency of FOXP3 + Regulatory T-Cells in Type 1 Diabetes Todd Brusko 1 , Clive Wasserfall 1 , Kieran McGrail 1 , Richard Schatz 1 , Hilla Lee Viener 2 , Desmond Schatz 2 , Michael Haller 2 , Jennifer Rockell 3 , Peter Gottlieb 3 , Michael Clare-Salzler 1 and Mark Atkinson 1 1 Department of Pathology, University of Florida, Gainesville, Florida 2 Department of Pediatrics, University of Florida, Gainesville, Florida 3 Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, Colorado Address correspondence and reprint requests to Mark A. Atkinson, PhD, Department of Pathology, College of Medicine, University of Florida, ARB-R3-128, 1600 SW Archer Rd., Gainesville, FL 32610-0275. E-mail: atkinson{at}ufl.edu Abstract Regulatory T-cells (Tregs) play a critical role in maintaining dominant peripheral tolerance. Previous characterizations of Tregs in type 1 diabetes have used antibodies against CD4 and α-chain of the interleukin-2 receptor complex (CD25). This report extends those investigations by the addition of a more lineage-specific marker for Tregs, transcription factor forkhead box P3 (FOXP3), in subjects with type 1 diabetes, their first-degree relatives, and healthy control subjects. With inclusion of this marker, two predominant populations of CD4 + CD25 + T-cells were identified: CD4 + CD25 + FOXP3 + as well as CD4 + FOXP3 − T-cells expressing low levels of CD25 (CD4 + CD25 LOW FOXP3 − ). In all study groups, the frequency of CD4 + CD25 + FOXP3 + cells was age independent, whereas CD4 + CD25 LOW FOXP3 − cell frequencies strongly associated with age. In terms of additional markers for delineating cells of Treg lineage, FOXP3 + cells were CD127 − to CD127 LOW whereas CD25 + cells were less restricted in their expression of this marker, with CD127 expressed across a continuum of levels. Importantly, no differences were observed in the frequency of CD4 + CD25 + FOXP3 + T-cells in individuals with or at varying degrees of risk for type 1 diabetes. These investigations suggest that altered peripheral blood frequencies of Tregs, as defined by the expression of FOXP3, are not specifically associated with type 1 diabetes and continue to highlight age as an important variable in analysis of immune regulation. APC, allophycocyanin CBC, complete blood count CD25, α-chain of the interleukin-2 receptor complex FITC, fluorescein isothiocyanate FOXP3, transcription factor forkhead box P3 GADA, GAD autoantibody IL, interleukin MHC, major histocompatibility complex PE, phycoerythrin Teff, CD4+CD25− effector T-cell Treg, CD4+CD25+FOXP3+ regulatory T-cell Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted November 27, 2006. Received September 6, 2006. DIABETES