A regulatory CD4+ T cell subset in the BB rat model of autoimmune diabetes expresses neither CD25 nor Foxp3
Authors
Hillebrands, Jan-LuukWhalen, 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 VirologyProgram in Molecular Medicine
Department of Medicine, Division of Diabetes
Document Type
Journal ArticlePublication Date
2006-11-23Keywords
Adoptive TransferAnimals
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
Metadata
Show full item recordAbstract
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.177.11.7820Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38201PubMed ID
17114453Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.177.11.7820