A crucial role of CD4 T cells as a functional source of CD154 in the initiation of insulin-dependent diabetes mellitus in the non-obese diabetic mouse
A crucial role of CD4 T cells as a functional source of CD154 in the initiation of insulin-dependent diabetes mellitus in the non-obese diabetic mouse
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DOI：
10.1093/intimm/dxg035
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发表时间：
2003-03-01
影响因子：
4.4
通讯作者：
Flavell, RA
中科院分区：
文献类型：
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作者：
Eshima, K;Mora, C;Flavell, RA
尽管 I 型（胰岛素依赖型）糖尿病 (T1DM) 中 CD4 T 细胞的关键需求已得到充分记录，但有关 CD4 T 细胞在 T1DM 发展中的确切作用的信息仍然有限。在这里，利用缺乏 CD154 的非肥胖糖尿病 (NOD) 小鼠 (CD154-KO/NOD)，我们确定了 CD4 T 细胞作为 CD154 的功能来源在 T1DM 起始中的强制性作用。如果没有 CD154，CD4 T 细胞就无法介导 NOD 小鼠疾病发展的帮助。事实上，CD4 T 细胞上 CD154 的完全表达似乎对于 T1DM 的正常自发发展至关重要，因为在 CD154(+/-) 小鼠中没有观察到糖尿病，其中大约一半的 CD4 T 细胞根本不表达 CD154，至少在它们 40 周龄时是这样。研究还表明，胰岛β细胞上CD80的转基因表达（据信为β细胞提供了启动对胰岛抗原特异性的细胞毒性T淋巴细胞的能力）并没有恢复CD154-KO/NOD小鼠的胰岛炎。总的来说，这些结果表明，CD4 T 细胞作为 CD154 的来源在 T1DM 中发挥着至关重要的作用，并且 CD154 在 CD4 T 细胞上在胰岛素炎中的作用可能不仅仅是通过激活携带胰岛抗原的抗原呈递细胞来促进自身反应性 CD8 T 细胞的启动和扩增。
Although the critical requirement of CD4 T cells in type I (insulin-dependent) diabetes mellitus (T1DM) has been well documented, information on the exact role(s) of CD4 T cells in T1DM development is still limited. Here, utilizing non-obese diabetic (NOD) mice deficient for CD154 (CD154-KO/NOD), we have identified a mandatory role of CD4 T cells as the functional source of CD154 in the initiation of T1DM. Without CD154, CD4 T cells were not capable of mediating help in disease development in NOD mice. In fact, full expression of CD154 on the CD4 T cells seems to be essential in the normal spontaneous development of T1DM, since no diabetes was observed in CD154(+/-) mice in which around half of CD4 T cells do not express CD154 at all, at least by the time they were 40 weeks old. It was also shown that transgenic expression of CD80 on beta cells of pancreatic islets, which is believed to provide beta cells with the ability to prime cytotoxic T lymphocytes specific for islet antigens, did not restore insulitis in CD154-KO/NOD mice. Taken collectively, these results indicated that CD4 T cells play a crucial role in T1DM as a source of CD154, and that the role of CD154 on CD4 T cells in insulitis may not be just to facilitate priming and expanding of auto-reactive CD8 T cells by activating antigen-presenting cells bearing islet antigens.