T-cell activation and receptor downmodulation precede deletion induced by mucosally administered antigen
T-cell activation and receptor downmodulation precede deletion induced by mucosally administered antigen
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DOI：
10.1172/jci10738
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发表时间：
2000-10-01
影响因子：
15.9
通讯作者：
Whitacre, CC
中科院分区：
文献类型：
--
作者：
Benson, JM;Campbell, KA;Whitacre, CC
在髓鞘碱性蛋白（MBP）T细胞受体（TCR）转基因（Tg）小鼠中，在口服施用MBP后，表征抗原特异性T细胞的命运。外周Th细胞在体内立即被激活，如通过上调CD69和增加的细胞因子应答（Th1和Th2）所示。同时，表面TCR表达减少，内部TCR水平增加。当在TCR下调期间受到实验性自身免疫性脑脊髓炎的挑战时，Tg小鼠受到保护免于疾病。为了在抗原喂养后的稍后时间表征Th细胞，有必要防止幼稚Tg细胞的胸腺释放。因此，在给药前切除成年Tg小鼠的胸腺。胸腺切除Tg小鼠的TCR表达返回MBP喂养后3天，然后最终下降与MBP特异性增殖和细胞因子反应（Th1型和Th2型）。这种下降与细胞凋亡的增加相关。总的来说，这些结果表明，高剂量的喂食抗原诱导早期T细胞活化和TCR下调，随后是无反应性的中间阶段和随后的缺失。
The fate of antigen-specific T cells was characterized in myelin basic protein (MBP) T-cell receptor (TCR) transgenic (Tg) mice after oral administration of MBP. Peripheral Th cells are immediately activated in vivo, as indicated by upregulation of CD69 and increased cytokine responses (Th1 and Th2). Concurrently, surface TCR expression diminishes and internal TCR levels increase. When challenged for experimental autoimmune encephalomyelitis during TCR downmodulation, Tg mice are protected from disease. To characterize Th cells at later times after antigen feeding, it was necessary to prevent thymic release of naive Tg cells. Therefore, adult Tg mice were thymectomized before treatment. TCR expression returns in thymectomized Tg mice 3 days after MBP feeding and then ultimately declines in conjunction with MBP-specific proliferation and cytokine responses (Th1-type and Th2-type). The decline correlates with an increase in apoptosis. Collectively, these results demonstrate that a high dose of fed antigen induces early T-cell activation and TCR downmodulation, followed by an intermediate stage of anergy and subsequent deletion.