Murine lymphokine-activated killer (LAK) cells: phenotypic characterization of the precursor and effector cells.
Murine lymphokine-activated killer (LAK) cells: phenotypic characterization of the precursor and effector cells.
复制标题
鼠淋巴因子激活杀伤 (LAK) 细胞：前体细胞和效应细胞的表型特征。
DOI：
10.4049/jimmunol.137.2.715
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发表时间：
1986
影响因子：
4.4
通讯作者：
S. Rosenberg
中科院分区：
文献类型：
--
作者：
J. C. Yang;J. Mulé;S. Rosenberg
在重组白细胞介素2 （RIL 2）中培养的小鼠和人淋巴细胞产生细胞毒性细胞（淋巴因子激活杀伤细胞[LAK]），它们能够溶解大量新鲜肿瘤细胞，但不能溶解新鲜的正常细胞。静脉给药这些细胞并同时给药RIL 2可以消除小鼠肺和肝转移灶。为了表征具有体外LAK活性的细胞，我们通过使用补体和针对淋巴细胞表面标记物的抗体或荧光激活的细胞分选裂解选定的亚群来细分小鼠淋巴细胞。在RIL 2孵育后，发现thy -1.2阴性脾细胞产生接近正常量的LAK活性。thy -1.2阳性脾细胞产生小而不一致的LAK细胞活性。ia阳性和表面免疫球蛋白阳性的脾细胞很少或没有LAK前体能力，并且似乎不是LAK激活所必需的。用抗亚洲苜蓿GM1 （anti-ASGM1）异源血清和补体治疗脾细胞可显著降低其产生LAK活性的能力。在效应期，细胞毒性细胞呈thy -1.2阳性，ia -阴性表型。将ia耗尽的细胞分为携带或不携带γ Fc受体（gamma FcR）的亚群。大多数细胞毒性存在于γ - fcr阳性细胞中。因此，小鼠LAK细胞的前体是既不携带T细胞表面标记物也不携带B细胞表面标记物的“空”淋巴细胞，但在体外产生Thy-1.2细胞表面标记物，这与RIL 2刺激后对新鲜肿瘤细胞产生裂解活性有关。
Murine and human lymphocytes incubated in recombinant interleukin 2 (RIL 2) generate a population of cytotoxic cells (lymphokine-activated killer cells [LAK]), which are able to lyse a wide array of fresh tumor cells but do not lyse fresh normal cells. Intravenous administration of these cells with the concomitant administration of RIL 2 can eliminate established pulmonary and hepatic metastases in mice. To characterize the cell that has in vitro LAK activity, we subdivided murine lymphocytes by lysing select subpopulations with the use of complement and antibodies against lymphocyte surface markers or by fluorescence-activated cell sorting. Thy-1.2-negative splenocytes were found to generate near normal amounts of LAK activity after RIL 2 incubation. Small and inconsistent LAK cell activity was generated from Thy-1.2-positive splenocytes. Ia-positive and surface immunoglobulin-positive splenocytes had little or no LAK precursor capability and did not appear to be necessary for LAK activation. Treatment of splenocytes with anti-asialo GM1 (anti-ASGM1) heterosera and complement markedly decreased their ability to generate LAK activity. At the effector stage, cytotoxic cells were of the Thy-1.2-positive, Ia-negative phenotype. Ia-depleted cells were separated into subpopulations bearing or not bearing the gamma Fc receptor (gamma FcR). The majority of cytotoxicity resided in gamma FcR-positive cells. Thus the precursors of murine LAK cells are "null" lymphocytes bearing neither T nor B cell surface markers but develop the Thy-1.2 cell surface marker in vitro, in association with the development of lytic activity for fresh tumor cells after stimulation by RIL 2.