Xu X, Chong A S
Department of General Surgery and Immunology/Microbiology, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
J Immunol. 1995 Dec 1;155(11):5241-8.
The cross-linking of low-affinity Fc gamma RIIIA on NK cells with specific mAbs or aggregated IgG stimulates both cytotoxic activity and cytokine production. In addition, the interaction of NK cells with certain tumor cells can also stimulate cytokine production and cytotoxic activity. The identity of the molecules on the tumor cell or NK cells involved in this stimulation currently has not been defined. We have reported previously that cross-linking of CD45 and the CD45RO isoform on IL-2-activated NK cells or the NK cell line NK3.3 results in the stimulation of IFN-gamma production. We report here that this effect is specific, because cross-linking of CD45 does not stimulate the expression of cytotoxic activity. Consistent with studies suggesting that cross-linking of CD45 results in reduced phosphatase activity, inhibition of tyrosine phosphatase activity by pharmacologic means also resulted in enhanced tyrosine kinase activity and, ultimately, increased IFN-gamma production. Biochemical analyses and immunofluorescence studies suggest that the tyrosine kinase associated with CD45 is p56lck and that cross-linking of CD45 results in the activation of p56lck. Thus, CD45 may regulate p56lck kinase, which initiates the cascade of intracellular tyrosine phosphorylation events that lead to IFN-gamma transcription and secretion in NK 3.3 cells.
用特异性单克隆抗体或聚集的IgG使自然杀伤细胞（NK细胞）上低亲和力的FcγRIIIA交联，可刺激细胞毒性活性和细胞因子的产生。此外，NK细胞与某些肿瘤细胞的相互作用也能刺激细胞因子的产生和细胞毒性活性。目前，尚不清楚参与这种刺激作用的肿瘤细胞或NK细胞上的分子是什么。我们之前报道过，在白细胞介素-2激活的NK细胞或NK细胞系NK3.3上，CD45与CD45RO异构体交联会刺激γ干扰素的产生。我们在此报告，这种效应具有特异性，因为CD45交联不会刺激细胞毒性活性的表达。与表明CD45交联会导致磷酸酶活性降低的研究一致，通过药理学方法抑制酪氨酸磷酸酶活性也会导致酪氨酸激酶活性增强，并最终增加γ干扰素的产生。生化分析和免疫荧光研究表明，与CD45相关的酪氨酸激酶是p56lck，并且CD45交联会导致p56lck激活。因此，CD45可能调节p56lck激酶，后者启动细胞内酪氨酸磷酸化事件的级联反应，从而导致NK 3.3细胞中γ干扰素的转录和分泌。
