AIMS/HYPOTHESIS: The LEW.1AR1-iddm rat is an animal model of spontaneous type 1 diabetes mellitus. This study analysed how adoptive transfer of selective T cell subpopulations affects the incidence of diabetes. METHODS: CD4(+) or CD8(+) T cells were isolated from diabetic LEW.1AR1-iddm rats or diabetes-resistant LEW.1AR1 rats. Cells were selectively transferred into athymic LEW.1AR1-Whn ( rnu ) or prediabetic LEW.1AR1-iddm rats. The animals were monitored for blood glucose, islet infiltration and immune cell composition of pancreas-draining lymph nodes. RESULTS: After adoptive transfer of CD4(+) T cells from diabetic LEW.1AR1-iddm rats into athymic LEW.1AR1-Whn ( rnu ) rats, 50% of the recipients developed diabetes. Transfer of CD8(+) T cells failed to induce diabetes. Only 10% of the athymic recipients became diabetic after co-transfer of CD4(+) and CD8(+) T cells. Adoptive transfer of CD8(+) T cells from LEW.1AR1 or diabetic LEW.1AR1-iddm rats into prediabetic LEW.1AR1-iddm rats significantly reduced the incidence of diabetes. In protected normoglycaemic animals regulatory CD8(+)/CD25(+) and CD4(+)/CD25(+) T cell subpopulations that were also FOXP3-positive accumulated in the pancreas-draining lymph nodes. In this lymphatic organ, gene expression of anti-inflammatory cytokines was significantly higher than in diabetic rats. CONCLUSIONS/ INTERPRETATION: Our results show that adoptive transfer of CD4(+) but not CD8(+) T cells from diabetic LEW.1AR1-iddm rats induced diabetes development. Importantly, CD8(+) T cells from diabetic LEW.1AR1-iddm rats and diabetes-resistant LEW.1AR1 rats provided protection against beta cell destruction. The accumulation of regulatory T cells in the pancreas-draining lymph nodes from protected rats indicates that transferred CD8(+) T cells may have beneficial effects in the control of beta cell autoimmunity.
AIMS/HYPOTHESIS: The LEW.1AR1-iddm rat is an animal model of spontaneous type 1 diabetes mellitus. This study analysed how adoptive transfer of selective T cell subpopulations affects the incidence of diabetes. METHODS:CD4(+) or CD8(+) T cells were isolated from diabetic LEW.1AR1-iddm rats or diabetes-resistant LEW.1AR1 rats. Cells were selectively transferred into athymic LEW.1AR1-Whn ( rnu ) or prediabetic LEW.1AR1-iddm rats. The animals were monitored for blood glucose, islet infiltration and immune cell composition of pancreas-draining lymph nodes. RESULTS: After adoptive transfer of CD4(+) T cells from diabetic LEW.1AR1-iddm rats into athymic LEW.1AR1-Whn ( rnu ) rats, 50% of the recipients developed diabetes. Transfer of CD8(+) T cells failed to induce diabetes. Only 10% of the athymic recipients became diabetic after co-transfer of CD4(+) and CD8(+) T cells. Adoptive transfer of CD8(+) T cells from LEW.1AR1 or diabetic LEW.1AR1-iddm rats into prediabetic LEW.1AR1-iddm rats significantly reduced the incidence of diabetes. In protected normoglycaemic animals regulatory CD8(+)/CD25(+) and CD4(+)/CD25(+) T cell subpopulations that were also FOXP3-positive accumulated in the pancreas-draining lymph nodes. In this lymphatic organ, gene expression of anti-inflammatory cytokines was significantly higher than in diabeticrats. CONCLUSIONS/ INTERPRETATION: Our results show that adoptive transfer of CD4(+) but not CD8(+) T cells from diabetic LEW.1AR1-iddm rats induced diabetes development. Importantly, CD8(+) T cells from diabetic LEW.1AR1-iddm rats and diabetes-resistant LEW.1AR1 rats provided protection against beta cell destruction. The accumulation of regulatory T cells in the pancreas-draining lymph nodes from protected rats indicates that transferred CD8(+) T cells may have beneficial effects in the control of beta cell autoimmunity.
Authors: S Lenzen; M Tiedge; M Elsner; S Lortz; H Weiss; A Jörns; G Klöppel; D Wedekind; C M Prokop; H J Hedrich Journal: Diabetologia Date: 2001-09 Impact factor: 10.122
Authors: U McKeever; J P Mordes; D L Greiner; M C Appel; J Rozing; E S Handler; A A Rossini Journal: Proc Natl Acad Sci U S A Date: 1990-10 Impact factor: 11.205
Authors: Volkert A L Huurman; Robert Hilbrands; Gabriëlle G M Pinkse; Pieter Gillard; Gaby Duinkerken; Pieter van de Linde; Petronella M W van der Meer-Prins; Minke F J Versteeg-van der Voort Maarschalk; Koen Verbeeck; Behrooz Z Alizadeh; Chantal Mathieu; Frans K Gorus; Dave L Roelen; Frans H J Claas; Bart Keymeulen; Daniel G Pipeleers; Bart O Roep Journal: PLoS One Date: 2008-06-18 Impact factor: 3.240
Authors: Zhijun Liu; Laura Cort; Ryan Eberwine; Thomas Herrmann; Jean H Leif; Dale L Greiner; Barak Yahalom; Elizabeth P Blankenhorn; John P Mordes Journal: Diabetes Date: 2012-02-24 Impact factor: 9.461
Authors: Henrike Lenzen; Maria Lünnemann; Andre Bleich; Michael P Manns; Ursula Seidler; Anne Jörns Journal: PLoS One Date: 2012-07-27 Impact factor: 3.240