Peterson E J, Clements J L, Ballas Z K, Koretzky G A
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Eur J Immunol. 1999 Jul;29(7):2223-32. doi: 10.1002/(SICI)1521-4141(199907)29:07<2223::AID-IMMU2223>3.0.CO;2-6.
The adapter protein SLP-76 is required for T cell development and TCR signal transduction. SLP-76 is also expressed in NK cells, yet splenic populations of NK cells develop normally in SLP-76-deficient mice. We examined the effects of SLP-76 deficiency upon cellular activation through studies of NK function in SLP-76(-/-) mice. This study presents evidence that NK populations in both spleen and liver of SLP-76(-/-) mice remain intact. Natural cytotoxic responses of SLP-76(-/-) splenocytes proceed in a manner comparable to those of wild-type control splenocytes. Similar to controls, SLP-76(-/-) splenocytes exhibit enhanced survival and augmented cytotoxic capacity after in vitro culture with IL-2. IL-2-stimulated SLP-76(-/-) splenocytes also retain normal antibody-dependent cellular cytotoxicity and the ability to secrete IFN-gamma in response to IL-12 stimulation. These results indicate that, unlike events stimulated by TCR engagement, signaling cascades engaged by IL-2 and IL-12 receptors, by Fc gammaRIIIA (which mediates antibody-dependent cellular cytotoxicity), and by natural cytotoxicity-associated receptors on murine NK cells can occur independently of SLP-76.
衔接蛋白SLP-76是T细胞发育和TCR信号转导所必需的。SLP-76也在自然杀伤（NK）细胞中表达，然而在缺乏SLP-76的小鼠中，脾脏中的NK细胞群体仍能正常发育。我们通过研究SLP-76基因敲除（SLP-76(-/-)）小鼠的NK功能，来检测SLP-76缺陷对细胞活化的影响。本研究表明，SLP-76(-/-)小鼠脾脏和肝脏中的NK细胞群体保持完整。SLP-76(-/-)脾细胞的天然细胞毒性反应与野生型对照脾细胞的反应方式相当。与对照组相似，SLP-76(-/-)脾细胞在与白细胞介素-2（IL-2）进行体外培养后，表现出更强的存活能力和增强的细胞毒性。经IL-2刺激的SLP-76(-/-)脾细胞也保持正常的抗体依赖性细胞毒性，以及在受到IL-12刺激时分泌γ干扰素（IFN-γ）的能力。这些结果表明，与TCR结合所刺激的事件不同，由IL-2和IL-12受体、FcγRIIIA（介导抗体依赖性细胞毒性）以及小鼠NK细胞上与天然细胞毒性相关的受体所引发的信号级联反应可以独立于SLP-76发生。
