MECHANISM OF IMMUNOLOGICALLY SPECIFIC KILLING OF TUMOR-CELLS BY MACROPHAGES
MECHANISM OF IMMUNOLOGICALLY SPECIFIC KILLING OF TUMOR-CELLS BY MACROPHAGES
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DOI：
10.1038/236168a0
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发表时间：
1972-01-01
期刊：
影响因子：
64.8
通讯作者：
ALEXANDER, P
中科院分区：
文献类型：
--
作者：
EVANS, R;ALEXANDER, P
感染活微生物的动物体内巨噬细胞抗微生物活性的增加通常是非特异性的1。相反，来自免疫动物的巨噬细胞的抗肿瘤活性已在体外被证明具有免疫特异性2,3。将要描述的实验可能会阐明这个悖论。他们表明，巨噬细胞杀死肿瘤细胞是由免疫特异性相互作用和随后的非特异性致死反应组成的。免疫巨噬细胞的杀菌作用也有类似的模式3。我们描述了获得对肿瘤细胞具有细胞毒性的免疫特异性巨噬细胞的三种方法3,5。这些是（1）来自适当免疫小鼠的腹膜腔（见下文）； (2)通过将非免疫巨噬细胞与来自超免疫小鼠的脾细胞接触进行体外“武装”，以及(3)通过将非免疫巨噬细胞暴露于用特异性抗原培养来自免疫小鼠的脾细胞时获得的无细胞上清液来进行体外“武装”。所有此类巨噬细胞在与特定抗原接触时都会发生转化（称为“激活”），从而使其能够发挥杀伤作用。与“激活的”巨噬细胞直接接触后靶细胞的实际破坏是非特异性的。此外，这种非特异性杀伤也可以通过“武装”针对结核杆菌（BCG）的巨噬细胞来证明，这些巨噬细胞在暴露于来自结核杆菌的溶解蛋白衍生物PPD后被“激活”，并且能够杀死肿瘤细胞。在最初的实验3,5中，将靶淋巴瘤细胞添加到“武装”巨噬细胞中，细胞毒性反应的免疫特异性阶段和非特异性阶段没有分开，而是依次发生（图1）。
THE increase in anti-microbial activity of macrophages which occurs in animals that have been infected with living microorganisms is frequently non-specific1. In contrast, the anti-tumour activity of macrophages from immunized animals has been demonstratedin vitroto be immunologically specific2,3. The experiments to be described may throw light on this paradox. They show that the killing of tumour cells by macrophages is made up of an immunologically specific interaction which is followed by a non-specific lethal reaction. A similar pattern has been described for the bactericidal action of immune macrophages3. We have described three ways of obtaining immunologically specific macrophages cytotoxic to tumour cells3,5. These are (1) from the peritoneal cavity of suitably immunized mice (see later); (2) “arming”in vitroby contact of non-immune macrophages with spleen cells from hyperimmunized mice, and (3) “arming”in vitroby exposure of non-immune macrophages to the cell-free supernatant obtained when spleen cells from immunized mice are cultured with the specific antigen. All such macrophages, on coming into contact with specific antigens, undergo a transformation (referred to as “activation”) which renders them capable of killing. The actual destruction of the target cell following direct contact with the “activated” macrophages is non-specific. Moreover, this non-specific killing may also be demonstrated by macrophages “armed” against tubercle bacilli (BCG) which are “activated” after exposure to the solubilized protein derivative from tubercli bacilli, PPD, and are able to kill tumour cells. In the original experiments3,5in which target lymphoma cells were added to “armed” macrophages the immunologically specific stage and the non-specific stage of the cytotoxic reactions were not separated and occurred sequentially (Fig. 1).