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Adaptive regulatory T cells (TR) reverse diabetes and persist as memory cells
Author(s) -
SummersTorres Daphne Mahriah,
Godebu Elana,
Bradley Linda M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1073.4
Subject(s) - adoptive cell transfer , il 2 receptor , foxp3 , nod , nod mice , microbiology and biotechnology , acquired immune system , interleukin 21 , immunology , biology , cytotoxic t cell , antigen presenting cell , t cell , immune system , endocrinology , diabetes mellitus , in vitro , biochemistry
In a previous study we used the type 1 non‐obese diabetic mouse model (NOD) to show that (TR) can be generated ex vivo from monoclonal islet‐specific CD4 cells by the combination of TCR signaling and TGFB1. These T cells express FoxP3, produce IL‐10 and TGFB1 and prevent the spontaneous induction of diabetes after adoptive transfer to NOD mice. Using allelically marked donor cells we now show that these TR cells can reverse overt diabetes if transferred early following the onset. Moreover, TR cells can also be induced from polyclonal CD4 cells from NOD mice. Following the adoptive transfer these TR cells can persist for more that one‐year and are able to maintain FoxP3 expression as well as production of IL‐10 and TGFB1. However they do not express CD25, which distinguishes them from the innate TR cells. We can identify adaptive TR cells in the lymphoid compartment and in pancreatic infiltrates of the protected mice. As memory cells these adaptive TR cells undergo homeostatic turnover and retain the capacity to respond to antigen challenge. Following re‐isolation as memory cells they transfer protection against diabetes to NOD recipients of diabetogenic effectors. The results indicate that adaptive regulatory CD4 cells can be homeostatically maintained as memory cells that can contribute to the long‐term control of diabetes, making them possible candidates for use as immunotherapeutic agents. NIH RO1 DK 59438; JDRF