通过选择性转移CD8 + T细胞预防LEW.1AR1 - iddm大鼠自发性免疫介导的糖尿病发展与胰腺引流淋巴结中的细胞因子转变有关。
Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes.
作者信息
Arndt T, Wedekind D, Weiss H, Tiedge M, Lenzen S, Hedrich H-J, Jörns A
机构信息
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
出版信息
Diabetologia. 2009 Jul;52(7):1381-90. doi: 10.1007/s00125-009-1348-1. Epub 2009 Apr 15.
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.
目的/假设：LEW.1AR1 - iddm大鼠是自发性1型糖尿病的动物模型。本研究分析了选择性T细胞亚群的过继转移如何影响糖尿病的发病率。
方法
从糖尿病LEW.1AR1 - iddm大鼠或抗糖尿病的LEW.1AR1大鼠中分离出CD4(+)或CD8(+) T细胞。将细胞选择性地转移到无胸腺的LEW.1AR1 - Whn (rnu)大鼠或糖尿病前期的LEW.1AR1 - iddm大鼠体内。监测动物的血糖、胰岛浸润情况以及胰腺引流淋巴结的免疫细胞组成。
结果
将糖尿病LEW.1AR1 - iddm大鼠的CD4(+) T细胞过继转移到无胸腺的LEW.1AR1 - Whn (rnu)大鼠后，50%的受体发生了糖尿病。CD8(+) T细胞的转移未能诱发糖尿病。在同时转移CD4(+)和CD8(+) T细胞后，只有10%的无胸腺受体发生了糖尿病。将LEW.1AR1或糖尿病LEW.1AR1 - iddm大鼠的CD8(+) T细胞过继转移到糖尿病前期的LEW.1AR1 - iddm大鼠中，可显著降低糖尿病的发病率。在血糖正常的受保护动物中，胰腺引流淋巴结中积累了同时也是FOXP3阳性的调节性CD8(+)/CD25(+)和CD4(+)/CD25(+) T细胞亚群。在这个淋巴器官中，抗炎细胞因子的基因表达明显高于糖尿病大鼠。
结论/解读：我们的结果表明，将糖尿病LEW.1AR1 - iddm大鼠的CD4(+)而非CD8(+) T细胞过继转移可诱发糖尿病的发展。重要的是，糖尿病LEW.1AR1 - iddm大鼠和抗糖尿病LEW.1AR1大鼠的CD8(+) T细胞可提供针对β细胞破坏的保护作用。受保护大鼠胰腺引流淋巴结中调节性T细胞的积累表明，转移的CD8(+) T细胞可能在控制β细胞自身免疫方面具有有益作用。
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