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.
Thomas
David C
DC
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, UK.
Mellanby
Richard J
RJ
Phillips
Jenny M
JM
Cooke
Anne
A
D000375:Aging / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000032:analysis*; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D013950:Thymus Gland / Q000276:immunology
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse