PMID:16301745

Citation	Chen, Z, Herman, AE, Matos, M, Mathis, D and Benoist, C (2005) Where CD4+CD25+ T reg cells impinge on autoimmune diabetes. J. Exp. Med. 202:1387-97
Abstract	Foxp3 is required for the generation and activity of CD4(+)CD25(+) regulatory T (T reg) cells, which are important controllers of autoimmunity, including type-1 diabetes. To determine where T reg cells affect the diabetogenic cascade, we crossed the Foxp3 scurfy mutation, which eliminates T reg cells, with the BDC2.5 T cell receptor (TCR) transgenic mouse line. In this model, the absence of T reg cells did not augment the initial activation or phenotypic characteristics of effector T cells in the draining lymph nodes, nor accelerate the onset of T cell infiltration of the pancreatic islets. However, this insulitis was immediately destructive, causing a dramatic progression to overt diabetes. Microarray analysis revealed that T reg cells in the insulitic lesion adopted a gene expression program different from that in lymph nodes, whereas T reg cells in draining or irrelevant lymph nodes appeared very similar. Thus, T reg cells primarily impinge on autoimmune diabetes by reining in destructive T cells inside the islets, more than during the initial activation in the draining lymph nodes.
Links	PubMed PMC2212985 Online version:10.1084/jem.20051409
Keywords	Animals; Diabetes Mellitus, Type 1/immunology; Diabetes Mellitus, Type 1/pathology; Forkhead Transcription Factors/deficiency; Forkhead Transcription Factors/genetics; Forkhead Transcription Factors/physiology; Lymph Nodes/immunology; Lymphocyte Activation/immunology; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Pancreas/immunology; Receptors, Interleukin-2/biosynthesis; T-Lymphocytes, Regulatory/immunology
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