An early age-related increase in the frequency of CD4+ Foxp3+ cells in BDC2.5NOD mice

Immunology. 2007 Aug;121(4):565-76. doi: 10.1111/j.1365-2567.2007.02604.x. Epub 2007 Apr 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Cells, Cultured
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / immunology
  • Forkhead Transcription Factors / analysis*
  • Immune Tolerance / immunology
  • Immunophenotyping
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Pancreas / immunology
  • Species Specificity
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / cytology*
  • Thymus Gland / immunology


  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse