Cutting edge: Defective NK cell activation in X-linked lymphoproliferative disease
Cutting edge: Defective NK cell activation in X-linked lymphoproliferative disease
复制标题
DOI：
10.4049/jimmunol.165.7.3549
复制
发表时间：
2000-10-01
影响因子：
4.4
通讯作者：
Tan, R
中科院分区：
文献类型：
--
作者：
Benoit, L;Wang, XX;Tan, R
X连锁淋巴增殖性疾病（XLP）的特征是对EB病毒存在选择性免疫缺陷。XLP的分子基础归因于信号淋巴细胞激活分子相关蛋白的突变，这是一种已知与淋巴细胞激活表面受体SLAM和2B4相关的细胞内分子。我们在SLAM相关蛋白中发现了一个单核苷酸突变，该突变影响携带突变基因男性的自然杀伤（NK）细胞功能。与正常对照相比，两名XLP患者的NK细胞和淋巴因子激活的杀伤细胞（LAK）的细胞毒性均显著降低。除了基线细胞毒性降低外，在正常对照中2B4的连接显著增强了NK细胞的裂解功能，但未能增强XLP患者NK细胞的细胞毒性。这些发现表明，SAP与2B4的结合对于最佳的NK/LAK细胞毒性是必要的，并意味着SAP/2B4信号传导的改变导致了在XLP中观察到的免疫功能障碍。
X-linked lymphoproliferative disease (XLP) is characterized by a selective immune deficiency to EBV, The molecular basis of XLP has been attributed to mutations of signaling lymphocytic activation molecule-associated protein, an intracellular molecule known to associate with the lymphocyte-activating surface receptors SLAM and 2B4. We have identified a single nucleotide mutation in SLAM-associated protein that affects the NK cell function of males carrying the mutated gene. In contrast to normal controls, both NK and lymphokine-activated killer cell cytotoxicity was significantly reduced in two XLP patients. In addition to decreased baseline cytotoxicity, ligation of 2B4 significantly augmented Ng lytic function in normal controls but failed to enhance the cytotoxicity of NK cells from XLP patients. These findings suggest that association of SAP with 2B4 is necessary for optimal NK/lymphokine-activated killer cytotoxicity and imply that alterations in SAP/2B4 signaling contribute to the immune dysfunction observed in XLP.