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

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.