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An early age‐related increase in the frequency of CD4 + Foxp3 + cells in BDC2·5NOD mice
Author(s) -
Thomas David C.,
Mellanby Richard J.,
Phillips Jenny M.,
Cooke Anne
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02604.x
Subject(s) - foxp3 , nod mice , biology , spleen , nod , genetically modified mouse , immunology , transgene , lymph , islet , in vivo , microbiology and biotechnology , medicine , endocrinology , immune system , genetics , diabetes mellitus , pathology , gene
Summary The role of regulatory T cells (Treg) in maintaining tolerance to self has been intensively scrutinized, particularly since the discovery of Foxp3 as a Treg‐specific transcription factor. The BDC2·5NOD transgenic mouse is an excellent model of immunoregulation because it has a very low incidence of diabetes despite a highly autoreactive T‐cell repertoire. It has previously been shown that reactivity against islets decreases with age in BDC2·5NOD mice. Here we show that there is a markedly higher frequency of Foxp3 + Treg in the CD4 + subset of 16–20‐week‐old mice compared with 4‐ or 8‐week‐old mice. This phenomenon can be observed in the spleen, thymus, pancreatic draining lymph nodes and the pancreas itself. We show that this early age‐related increase in the frequency of Foxp3 + cells does not occur in wild‐type NOD, BALB/c or C57BL/6 mice. Further, we show that, in contrast to some reports on Treg in wild‐type NOD mice, the suppressive function of BDC2·5NOD Treg from 16‐ to 20‐week‐old mice is intact and comparable to that from 4‐ to 8‐week‐old mice both in vitro and in vivo . Our data offer insights into the long‐term protection of BDC2·5NOD mice from diabetes and an explanation for the age‐related decrease in anti‐islet responses seen in BDC2·5NOD mice.