Albright J W, Albright J F
Proc Natl Acad Sci U S A. 1983 Oct;80(20):6371-5. doi: 10.1073/pnas.80.20.6371.
Natural cell-mediated cytotoxicity may be critical in the resistance displayed by animals and humans to tumors and various pathogenic microorganisms. Because the frequency of tumors and infections increases markedly in aging populations, we have compared the natural killer (NK) competence of lymphoid tissues (spleen, bone marrow) and of peritoneal cells of young adult and aged mice. Spontaneous NK activity was much lower, and the rate of target cell lysis was much less, in aged mice. The level of NK activity was only modestly increased in old, compared to young, mice when they were exposed to Trypanosoma musculi, an organism that provides strong stimulation of NK activity. Restricted NK activity of aged mice was not attributable to suppressor cells. The NK effector cells in old mice were characterized as being nonadherent to plastic, completely susceptible to lysis by complement plus an antiserum against specificity NK 1.2, and only slightly affected by treatment with antiserum against specificity Thy-1.2. Two indirect methods were employed to assess the relative frequency of splenic NK cells at the time of maximal stimulation by T. musculi: a cytotoxicity assay with antiserum against NK 1.2 and a binding assay involving monolayers of YAC-1 tumor target cells. Similar results were obtained in both assays, indicating that at maximal stimulation about 10% of the total spleen cells of both young and old mice were NK cells. We conclude (cautiously) that the functional efficiency of aged NK cells is impaired and that this defect may account, in part, for reduced ability of aged individuals to resist certain types of cancer and certain pathogenic microorganisms.
天然细胞介导的细胞毒性在动物和人类对肿瘤及各种病原微生物所表现出的抵抗力中可能至关重要。由于在老龄人群中肿瘤和感染的发生率显著增加，我们比较了年轻成年小鼠和老龄小鼠的淋巴组织（脾脏、骨髓）及腹腔细胞的自然杀伤（NK）能力。老龄小鼠的自发NK活性低得多，靶细胞裂解率也低得多。与年轻小鼠相比，老龄小鼠在接触对NK活性有强烈刺激作用的小鼠锥虫时，NK活性水平仅适度增加。老龄小鼠受限的NK活性并非归因于抑制细胞。老龄小鼠的NK效应细胞的特征为不黏附于塑料，对补体加抗特异性NK 1.2抗血清的裂解完全敏感，且仅受到抗特异性Thy-1.2抗血清处理的轻微影响。采用两种间接方法评估在受到小鼠锥虫最大刺激时脾NK细胞的相对频率：用抗NK 1.2抗血清进行的细胞毒性测定以及涉及YAC-1肿瘤靶细胞单层的结合测定。两种测定均获得相似结果，表明在最大刺激时，年轻和老龄小鼠的脾细胞总数中约10%为NK细胞。我们（谨慎地）得出结论，老龄NK细胞的功能效率受损，且这一缺陷可能部分解释了老龄个体抵抗某些类型癌症和某些病原微生物能力的下降。
