LYMPHOPROLIFERATIVE DISORDERS WITH EARLY LETHALITY IN MICE DEFICIENT IN CTLA-4
LYMPHOPROLIFERATIVE DISORDERS WITH EARLY LETHALITY IN MICE DEFICIENT IN CTLA-4
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DOI：
10.1126/science.270.5238.985
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发表时间：
1995-11-10
期刊：
影响因子：
56.9
通讯作者：
MAK, TW
中科院分区：
文献类型：
--
作者：
WATERHOUSE, P;PENNINGER, JM;MAK, TW
细胞表面分子CTLA-4在调节T细胞活化中的作用一直存在争议。在这里，CTLA-4缺陷小鼠的淋巴结和脾脏积累了具有上调的活化标志物的T细胞母细胞。这些原始细胞也浸润肝、心、肺和胰腺组织，血清免疫球蛋白含量升高。小鼠在3至4周龄时总是处于濒死状态。尽管CTLA-4缺陷型T细胞在通过T细胞受体刺激时自发且强烈地增殖，但它们对由Fas受体的交联和γ辐射诱导的细胞死亡敏感。因此，CTLA-4充当T细胞活化的负调节剂，并且对于控制淋巴细胞稳态至关重要。
The role of the cell-surface molecule CTLA-4 in the regulation of T cell activation has been controversial. Here, lymph nodes and spleens of CTLA-4-deficient mice accumulated T cell blasts with up-regulated activation markers. These blast cells also infiltrated liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin were elevated. The mice invariably became moribund by 3 to 4 weeks of age. Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation. Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis.