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    A regulatory CD4+ T cell subset in the BB rat model of autoimmune diabetes expresses neither CD25 nor Foxp3

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    Authors
    Hillebrands, Jan-Luuk
    Whalen, Barbara J.
    Visser, Jeroen T. J.
    Koning, Jasper
    Bishop, Kenneth D.
    Leif, Jean
    Rozing, Jan
    Mordes, John P.
    Greiner, Dale L.
    Rossini, Aldo A.
    UMass Chan Affiliations
    Program in Immunology and Virology
    Program in Molecular Medicine
    Department of Medicine, Division of Diabetes
    Document Type
    Journal Article
    Publication Date
    2006-11-23
    Keywords
    Adoptive Transfer
    Animals
    Antigens, CD45
    Autoimmune Diseases
    Cell Proliferation
    Diabetes Mellitus, Type 1
    Flow Cytometry
    Forkhead Transcription Factors
    Interleukin-2 Receptor alpha Subunit
    Protein Tyrosine Phosphatase, Non-Receptor Type 1
    Rats
    Rats, Inbred BB
    Reverse Transcriptase Polymerase Chain Reaction
    T-Lymphocyte Subsets
    T-Lymphocytes, Regulatory
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    https://doi.org/10.4049/jimmunol.177.11.7820
    Abstract
    Biobreeding (BB) rats model type 1 autoimmune diabetes (T1D). BB diabetes-prone (BBDP) rats develop T1D spontaneously. BB diabetes-resistant (BBDR) rats develop T1D after immunological perturbations that include regulatory T cell (Treg) depletion plus administration of low doses of a TLR ligand, polyinosinic-polycytidylic acid. Using both models, we analyzed CD4+CD25+ and CD4+CD45RC- candidate rat Treg populations. In BBDR and control Wistar Furth rats, CD25+ T cells comprised 5-8% of CD4+ T cells. In vitro, rat CD4+CD25+ T cells were hyporesponsive and suppressed T cell proliferation in the absence of TGF-beta and IL-10, suggesting that they are natural Tregs. In contrast, CD4+CD45RC(-) T cells proliferated in vitro in response to mitogen and were not suppressive. Adoptive transfer of purified CD4+CD25+ BBDR T cells to prediabetic BBDP rats prevented diabetes in 80% of recipients. Surprisingly, CD4+CD45RC-CD25- T cells were equally protective. Quantitative studies in an adoptive cotransfer model confirmed the protective capability of both cell populations, but the latter was less potent on a per cell basis. The disease-suppressing CD4+CD45RC-CD25- population expressed PD-1 but not Foxp3, which was confined to CD4+CD25+ cells. We conclude that CD4+CD25+ cells in the BBDR rat act in vitro and in vivo as natural Tregs. In addition, another population that is CD4+CD45RC-CD25- also participates in the regulation of autoimmune diabetes.
    Source

    J Immunol. 2006 Dec 1;177(11):7820-32.

    DOI
    10.4049/jimmunol.177.11.7820
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/38201
    PubMed ID
    17114453
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.177.11.7820
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