Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse
Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse
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DOI：
10.1073/pnas.121169698
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发表时间：
2001-06-05
影响因子：
11.1
通讯作者：
Sarvetnick, N
中科院分区：
文献类型：
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作者：
Shi, FD;Flodström, M;Sarvetnick, N
据报道，包括非肥胖糖尿病 (NOD) 小鼠在内的几种易患自身免疫的小鼠品系中，CD1 限制性自然杀伤 T 细胞存在定量和定性缺陷。这些缺陷被认为与自发性自身免疫的出现有关。在这里，我们证明，与 CD1d(+/-) 和 CD1d(+/+) 同窝小鼠相比，CD1d-null NOD 和 CD1d-null NOD/BDC2.5 T 细胞受体转基因小鼠的糖尿病发病加速且发病率增加。疾病的加速似乎不是由于 T 辅助细胞 (Th)1/Th2 平衡的变化造成的，因为从野生型和 CD1d-null 小鼠的淋巴器官和胰岛纯化的淋巴细胞分泌等量的刺激后的 IFN-γ 和 IL-4。相比之下，CD1d 缺失小鼠的胰腺含有明显更高数量的表达趋化因子受体 CCR4 的活化记忆 T 细胞。值得注意的是，这些 T 细胞的存在与破坏性胰岛炎增加的免疫组织化学证据相关。因此，CD1d 限制性 T 细胞对于调节 NOD 小鼠的自发疾病过程至关重要。
Quantitative and qualitative defects in CD1-restricted natural killer T cells have been reported in several autoimmune-prone strains of mice, including the nonobese diabetic (NOD) mouse. These defects are believed to be associated with the emergence of spontaneous autoimmunity. Here we demonstrate that both CD1d-null NOD and CD1d-null NOD/BDC2.5 T cell receptor transgenic mice have an accelerated onset and increased incidence of diabetes when compared with CD1d(+/-) and CD1d(+/+) littermates, The acceleration of disease did not seem to result from changes in the T helper (Th)1/Th2 balance because lymphocytes purified from lymphoid organs and pancreatic islets of wild-type and CD1d-null mice secreted equivalent amounts of IFN-gamma and IL-4 after stimulation. In contrast, the pancreata of CD1d-null mice harbored significantly higher numbers of activated memory T cells expressing the chemokine receptor CCR4, Notably, the presence of these T cells was associated with immunohistochemical evidence of increased destructive insulitis, Thus, CD1d-restricted T cells are critically important for regulation of the spontaneous disease process in NOD mice.