T-CELL-MEDIATED INHIBITION OF THE TRANSFER OF AUTOIMMUNE DIABETES IN NOD MICE

T-CELL-MEDIATED INHIBITION OF THE TRANSFER OF AUTOIMMUNE DIABETES IN NOD MICE
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DOI:
10.1084/jem.169.5.1669
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发表时间:
1989-05-01
影响因子:
15.3
通讯作者:
BACH, JF
BACH, JF
中科院分区:
医学1区
文献类型:
--
作者:
BOITARD, C;YASUNAMI, R;BACH, JF

文献摘要

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非肥胖型糖尿病(NOD)小鼠最近被引入作为胰岛素依赖型糖尿病的模型。在该模型中,调节性T细胞在抗胰腺自身免疫发展中的作用尚不清楚。为了评估抑制现象的存在,我们使用疾病转移的脾细胞从糖尿病NOD小鼠到预照射的成年受体作为加速疾病的模型。通过检测非糖尿病NOD小鼠淋巴细胞对辐射受体中糖尿病转移的保护作用,检测抑制现象。通过用非糖尿病NOD供体的脾细胞重建受体来延迟糖尿病的转移。对糖尿病转移的最大保护作用来自8周龄非糖尿病雌性NOD小鼠的脾细胞。耗竭实验表明,这种保护作用依赖于CD4+细胞。保护也检测到非糖尿病NOD小鼠的胸腺细胞和脾细胞赋予的保护被废除的非糖尿病女性,但不是男性,NOD捐助者在3周龄的胸腺切除术。这些发现表明,依赖于胸腺存在的抑制性CD4+ T细胞可能会延迟糖尿病易感NOD雌性小鼠的糖尿病发作。
The nonobese diabetic (NOD) mouse has recently been introduced as a model for insulin-dependent diabetes mellitus. The role of regulatory T cells in the development of antipancreatic autoimmunity in this model remains unclear. To evaluate the presence of suppressive phenomena, we used disease transfer by spleen cells from diabetic NOD mice into preirradiated adult recipients as a model for accelerated disease. Suppressor phenomena were detected by testing the protection afforded by lymphoid cells from nondiabetic NOD mice against diabetes transfer in irradiated recipients. Transfer of diabetes was delayed by reconstituting recipients with spleen cells from nondiabetic NOD donors. The greatest protection against diabetes transfer was conferred by spleen cells from 8-wk-old nondiabetic female NOD mice. Depletion experiments showed that the protection was dependent on CD4+ cells. Protection was also detected within thymic cells from nondiabetic NOD mice and protection conferred by spleen cells was abrogated by thymectomy of nondiabetic female, but not male, NOD donors at 3 wk of age. These findings indicate that suppressive CD4+ T cells that are dependent on the presence of the thymus may delay the onset of diabetes in female diabetes-prone NOD mice.