title: No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes.
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 alpha-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.
authors.affiliation: Department of Pathology, College of Medicine, University of Florida, 1600 SW Archer Rd., Gainesville, FL 32610-0275, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Brusko
authors.forename: Clive
authors.initials: C
authors.lastname: Wasserfall
authors.forename: Kieran
authors.initials: K
authors.lastname: McGrail
authors.forename: Richard
authors.initials: R
authors.lastname: Schatz
authors.forename: Hilla Lee
authors.initials: HL
authors.lastname: Viener
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
authors.forename: Michael
authors.initials: M
authors.lastname: Haller
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rockell
authors.forename: Peter
authors.initials: P
authors.lastname: Gottlieb
authors.forename: Michael
authors.initials: M
authors.lastname: Clare-Salzler
authors.forename: Mark
authors.initials: M
authors.lastname: Atkinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging; D015415:Biomarkers; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1