Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis.
Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis.
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DOI：
10.4049/jimmunol.145.10.3194
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发表时间：
1990-11
影响因子：
4.4
通讯作者：
Michael J. Robertson;Michael A. Caligiuri;Thomas J. Manley;H. Levine;Jerome Ritz
中科院分区：
文献类型：
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作者：
Michael J. Robertson;Michael A. Caligiuri;Thomas J. Manley;H. Levine;Jerome Ritz
细胞粘附分子（CAM）参与淋巴细胞、辅助细胞和靶细胞之间的相互作用，这些相互作用在有效免疫应答的产生中至关重要。为了表征CAM参与NK和淋巴因子激活的杀伤细胞（LAK）的活动，我们研究了几种CAM的表达新鲜分离的人NK细胞和体外用IL-2激活的NK细胞，并将其与T淋巴细胞在类似条件下的CAM表达进行比较。新鲜分离的人NK细胞均为LFA-3（CD 58）+，表达的LFA-1（CD 11 a/CD 18）表面水平是静息T淋巴细胞的2 - 3倍。更多的NK细胞比T细胞也表达表型检测水平的细胞间粘附分子-1（CD 54）。与IL-2体外孵育后，人NK细胞显示出CD 11 a/CD 18、CD 2、CD 54、CD 58和NK细胞相关Ag NKH-1（CD 56）的表面水平增加了4 - 6倍。此外，基本上所有NK细胞在暴露于IL-2后3天内均变为CD 54+。在与IL-2孵育后，T细胞没有表现出相当的CAM上调。NK细胞CAM表达的增加与E：T细胞结合物的形成增强、NK敏感靶点的杀伤增强以及先前NK抗性靶点的细胞毒性诱导（LAK活性）相关。外源性IL-2诱导的LAK活性可被抗CD 2、抗CD 11 a或抗CD 54抗体部分抑制，而抗CD 2和抗CD 11 a抗体联合使用几乎完全消除。这些研究表明，CAM在NK细胞溶解的调节中起着重要作用，CAM表达的变化可能会改变激活的NK效应子的靶细胞特异性。
Cell adhesion molecules (CAM) participate in interactions between lymphocytes, accessory cells, and target cells that are critical in the generation of effective immune responses. To characterize the involvement of CAM in NK and lymphokine activated killer (LAK) activities, we examined the expression of several CAM by freshly isolated human NK cells and by NK cells activated in vitro with IL-2, and compared this to CAM expression by T lymphocytes under similar conditions. Freshly isolated human NK cells were uniformly LFA-3 (CD58)+ and expressed two to three-fold higher surface levels of LFA-1 (CD11a/CD18) than resting T lymphocytes. More NK cells than T cells also expressed phenotypically detectable levels of intercellular adhesion molecule-1 (CD54). After in vitro incubation with IL-2, human NK cells demonstrated four- to sixfold increases in surface levels of CD11a/CD18, CD2, CD54, CD58, and the NK cell-associated Ag NKH-1 (CD56). Furthermore, essentially all NK cells became CD54+ within 3 days of exposure to IL-2. T cells did not demonstrate comparable up-regulation of CAM after incubation with IL-2. Increases in NK cell CAM expression were associated with enhanced formation of E:T cell conjugates, enhanced killing of NK-sensitive targets, and the induction of cytotoxicity for previously NK-resistant targets (LAK activity). The LAK activity induced by exogenous IL-2 could be partially inhibited by anti-CD2, anti-CD11a, or anti-CD54 antibodies and almost completely abrogated by anti-CD2 and anti-CD11a in combination. These studies suggest that CAM play a central role in the regulation of NK cytolysis, and that changes in CAM expression may alter the target cell specificity of activated NK effectors.