Cook J L, Iklé D N, Routes B A
Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
J Immunol. 1995 Dec 15;155(12):5512-8.
Newborn nude rats are NK cell deficient and highly susceptible to tumor induction by NK-susceptible, E1A oncogene-expressing, BHK-21 sarcoma cells, whereas adults have normal NK activity and are tumor resistant. This model of NK cell-related tumor rejection was used to characterize age-related functional maturation of NK cells during nude rat ontogeny. Small numbers of cytolytic incompetent, NKR-P1+ cells were detected in the spleens of newborns. During the first month of life, there was an age-related increase in the numbers of splenic NK cells, followed by a stepwise maturation in their cytolytic competence. Three functional stages in NK cell cytolytic activity were apparent. A nonlytic newborn stage was followed by a transitional stage, during which absent or relatively weak spontaneous cytolytic activity was augmented by prolonged NK cell exposure to susceptible target cells. In the final stage, both spontaneous and augmented cytolytic activity increased toward the adult level that was attained by 4 wk of age. The data suggest the existence of a transient stage in NK cell ontogeny when triggering through the NKR-P1 molecule is functionally immature, and confirm the importance of a cytolytic competent, NK cell response for nude rat rejection of E1A oncogene-expressing tumor cells.
新生裸鼠缺乏自然杀伤（NK）细胞，对表达E1A癌基因的NK敏感型BHK - 21肉瘤细胞诱导的肿瘤高度易感，而成年裸鼠具有正常的NK活性且对肿瘤具有抗性。这种与NK细胞相关的肿瘤排斥模型被用于表征裸鼠个体发育过程中NK细胞与年龄相关的功能成熟情况。在新生裸鼠的脾脏中检测到少量细胞溶解能力不足的NKR - P1 +细胞。在生命的第一个月，脾脏NK细胞数量随年龄增加，随后其细胞溶解能力逐步成熟。NK细胞的细胞溶解活性有三个功能阶段。首先是无溶解能力的新生阶段，接着是过渡阶段，在此阶段，通过延长NK细胞与敏感靶细胞的接触时间，原本缺失或相对较弱的自发细胞溶解活性会增强。在最后阶段，自发和增强的细胞溶解活性都朝着4周龄时达到的成年水平增加。数据表明在NK细胞个体发育过程中存在一个短暂阶段，此时通过NKR - P1分子触发的功能不成熟，并证实了具有细胞溶解能力的NK细胞反应对于裸鼠排斥表达E1A癌基因的肿瘤细胞的重要性。
