Characteristics of rat CD4(+)CD25(+) T cells and their ability to prevent not only diabetes but also insulitis in an adoptive transfer model in BB rats.
Human and mouse CD4(+)CD25(+) T cells have been intensively studied through the last decade. However, little is known about this subset in other species. This study describes the phenotype of rat CD4(+)CD25(+) Foxp3(+) T cells and the site in which they exert regulation in a transfer-induced autoimmune diabetes model. Several proteins and mRNAs are up-regulated in unstimulated rat CD4(+)CD25(+) T cells compared with CD4(+)CD25(-) T cells, including Foxp3, Lag-3, CD80, interleukin 10 (IL-10) and CTLA-4. To investigate CD4(+)CD25(+) T cells in vivo, we transferred three million diabetogenic T cells either alone or in combination with two million CD4(+)CD25(+) T cells to 30-day-old BB rats. The pancreas and the pancreatic lymph nodes were examined as two potential regulatory sites. Time-course analysis of pancreatic histology following diabetogenic T-cell transfers revealed insulitis from about 14 days after transfer. By contrast, rats receiving both diabetogenic T cells and CD4(+)CD25(+) T cells had no insulitis at any time. Moreover, the frequency of diabetogenic T cells in the pancreatic lymph nodes 2 days after transfer was significantly reduced in rats receiving both subsets. These data indicate that the primary site of T-cell regulation is in the draining lymph nodes and not the pancreas in our model.
Holm
T L
TL
Hagedorn Research Institute, Gentofte, Denmark.
Lundsgaard
D
D
Markholst
H
H
D019264:Adoptive Transfer; D000818:Animals; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D007249:Inflammation; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D010179:Pancreas / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011913:Rats, Inbred BB; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation*
D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D015375:Receptors, Interleukin-2