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    Signatures of human regulatory T cells: an encounter with old friends and new players.

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    Authors
    Pfoertner, Susanne
    Jeron, Andreas
    Probst-Kepper, Michael
    Guzman, Carlos A
    Hansen, Wiebke
    Westendorf, Astrid M
    Toepfer, Tanja
    Schrader, Andres J
    Franzke, Anke
    Buer, Jan
    Geffers, Robert
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    Issue Date
    2006
    
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    Abstract
    BACKGROUND: Naturally occurring CD4+ CD25+ regulatory T cells (TReg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on TReg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined. RESULTS: To improve characterization of human TReg cells, we compiled a unique microarray consisting of 350 TReg cell associated genes (Human TReg Chip) based on whole genome transcription data from human and mouse TReg cells. TReg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in TReg cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3, CTLA4, and CCR7) that are known to be involved in TReg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human TReg cells (including LGALS3, TIAF1, and TRAF1). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human TReg cell function. CONCLUSION: The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human TReg cells. The Human TReg Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate TReg cells under physiologic and diseased conditions.
    Citation
    Genome Biol. 2006, 7(7):R54
    URI
    http://hdl.handle.net/10033/14544
    DOI
    10.1186/gb-2006-7-7-r54
    PubMed ID
    16836768
    Type
    Article
    Language
    en
    ISSN
    1465-6914
    ae974a485f413a2113503eed53cd6c53
    10.1186/gb-2006-7-7-r54
    Scopus Count
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