Elder M E, Lin D, Clever J, Chan A C, Hope T J, Weiss A, Parslow T G
Department of Pediatrics, University of California, San Francisco 94143-0110.
Science. 1994 Jun 10;264(5165):1596-9. doi: 10.1126/science.8202712.
A homozygous mutation in the kinase domain of ZAP-70, a T cell receptor-associated protein tyrosine kinase, produced a distinctive form of human severe combined immunodeficiency. Manifestations of this disorder included profound immunodeficiency, absence of peripheral CD8+ T cells, and abundant peripheral CD4+ T cells that were refractory to T cell receptor-mediated activation. These findings demonstrate that ZAP-70 is essential for human T cell function and suggest that CD4+ and CD8+ T cells depend on different intracellular signaling pathways to support their development or survival.
ZAP-70（一种与T细胞受体相关的蛋白酪氨酸激酶）激酶结构域中的纯合突变导致了一种独特形式的人类严重联合免疫缺陷。这种疾病的表现包括严重免疫缺陷、外周血CD8⁺ T细胞缺失，以及大量对外周血T细胞受体介导的激活具有抗性的外周血CD4⁺ T细胞。这些发现表明ZAP-70对人类T细胞功能至关重要，并提示CD4⁺ 和CD8⁺ T细胞依赖不同的细胞内信号通路来支持其发育或存活。
