ESSENTIAL ROLE FOR ZAP-70 IN BOTH POSITIVE AND NEGATIVE SELECTION OF THYMOCYTES
ESSENTIAL ROLE FOR ZAP-70 IN BOTH POSITIVE AND NEGATIVE SELECTION OF THYMOCYTES
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DOI：
10.1038/376435a0
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发表时间：
1995-08-03
期刊：
影响因子：
64.8
通讯作者：
LOH, DY
中科院分区：
文献类型：
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作者：
NEGISHI, I;MOTOYAMA, N;LOH, DY
在胸腺发育过程中，能够识别与自身主要组织相容性复合体(MHC)相关的外来抗原的T细胞被选择存活(阳性选择)，而自身反应性T细胞被排除(阴性选择)。这两个选择性事件都是由T细胞受体(TCR)和多肽-MHC复合体(1)之间的相互作用介导的，但导致细胞存活或死亡的信号通路仍不清楚。ZAP-70是一种与TCR信号亚单位(CD3和Zeta)相关的蛋白酪氨酸激酶(PTK)，表达于T细胞和自然杀伤细胞(2)。研究表明，ZAP-70在T细胞的激活(2-5)和发育(6-8)过程中起着至关重要的作用。在这里，我们表明，缺乏ZAP-70的小鼠既没有CD4也没有CD8单阳性T细胞，但人类ZAP-70重建了CD4和CDS单阳性群体。此外，ZAP-70(-/-)胸腺细胞不被多肽抗原删除。在没有ZAP-70的情况下，自然杀伤细胞的功能是完整的。这些数据表明，ZAP-70是胸腺选择CD4和CD8谱系的中心信号分子。
DURING thymic development, T cells that can recognize foreign antigen in association with self major histocompatibility complex (MHC) are selected for survival (positive selection) and autoreactive T cells are eliminated (negative selection). Both of these selective events are mediated by interaction between the T-cell receptor (TCR) and the peptid-MHC complex(1) But the signalling pathways that lead to cell survival or to cell death are still unclear. ZAP-70 is a protein tyrosine kinase (PTK) that is associated with the TCR signalling subunits (CD3 and zeta) and is expressed in T cells and natural killer cell(2). It has been shown that ZAP-70 plays a crucial role in T-cell activation(2-5) and development(6-8). Here we show that mice lacking ZAP-70 had neither CD4 nor CD8 single-positive T cells, but human ZAP-70 reconstituted both CD4 and CDS single-positive populations. Moreover, ZAP-70(-/-) thomocytes were not deleted by peptide antigens. Natural killer cell function was intact in the absence of ZAP-70. These data suggest that ZAP-70 is a central signalling molecule during thymic selection for CD4 and CD8 lineage.