SAP and SLAM expression in anti‐CD3 activated lymphocytes correlates with cytotoxic activity
SAP and SLAM expression in anti‐CD3 activated lymphocytes correlates with cytotoxic activity
复制标题
抗 CD3 激活淋巴细胞中 SAP 和 SLAM 的表达与细胞毒活性相关
作者：
Stefan Mehrle;S. Frank;Jan Schmidt;I. Schmidt;A. Märten
信号淋巴细胞激活分子(SLAM)相关蛋白(SAP)是一种在X连锁淋巴增生性(XLP)疾病患者中突变的小蛋白。XLP病患者会受到致命的EBV感染和恶性B细胞淋巴瘤的影响。B细胞淋巴瘤风险的增加被认为是由于T细胞对B细胞增殖的免疫监控受损所致。在这项研究中，我们研究了SLAM和SAP在激活具有细胞毒活性的效应细胞--细胞因子诱导的杀伤(CIK)细胞中的作用。细胞因子诱导的杀伤(CIK)细胞是通过TCR的非特异性刺激和外源IL-2的加入而产生的。准备后1天(+1天)的TCR激动性激活导致细胞激活，在蛋白质和mRNA水平上都可以看到+6天的SLAM峰值，并且在膜上可检测到SLAM。这种SLAM表达的增加与SAP在mRNA和蛋白质水平上的表达显著相关。细胞毒活性在观察到的SAP和SLAM峰值后1天达到顶峰。在那个时间点，IL-10的分泌，在培养的早期是很高的，但下降了。总之，用激动型抗CD3抗体和外源性IL-2激活外周血细胞以产生CIK细胞，可在TCR刺激后5天显著激活SLAM和SAP。这一峰值与对肿瘤细胞的细胞毒活性有关。SLAM和SAP的表达可能在细胞毒效应细胞的激活中起重要作用。
Signalling lymphocyte activation molecule (SLAM)‐associated protein (SAP) is a small protein that is mutant in humans with X‐linked lymphoproliferative (XLP) disease. Patients with XLP disease are affected by fatal EBV infection and malignant B‐cell lymphomas. The increased risk for B‐cell lymphomas is suggested to result from impaired immunosurveillance of B‐cell proliferation by T cells. In this study, we investigated the role of SLAM and SAP in activation of effector cells with cytotoxic activity, cytokine‐induced killer (CIK) cells, which are generated by non‐specific stimulation of the TCR and addition of exogenous IL‐2. Agonistic TCR activation 1 day after preparation (day +1) resulted in cell activation, with a peak of SLAM on day +6 visible at both the protein and mRNA level as well as membrane detectable SLAM. This increase in SLAM expression correlated significantly with SAP expression at the mRNA level as well as at the protein level. Cytotoxic activity peaked 1 day after the observed SAP and SLAM peaks. At that point in time, IL‐10 secretion, which was high during the early days of culture, decreased. In conclusion, activation of peripheral blood cells with agonistic anti‐CD3 antibody and exogenous IL‐2, as used for generation of CIK cells, results in significant SLAM and SAP activation 5 days after TCR stimulation. This peak correlates with cytotoxic activity against tumour cells. Expression of SLAM and SAP seems to be important in the activation of cytotoxic effector cells.
影响因子：
20.3
作者：
Baker, J;Verneris, MR;Negrin, RS
通讯作者：
Negrin, RS