Loss of resistance to a highly immunogenic tumor with age corresponds to the decline of CD8 T cell activity
Loss of resistance to a highly immunogenic tumor with age corresponds to the decline of CD8 T cell activity
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DOI：
10.1097/00002371-199807000-00008
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发表时间：
1998-07-01
影响因子：
3.9
通讯作者：
Haque, S
中科院分区：
文献类型：
--
作者：
Flood, PM;Liu, XM;Haque, S
许多紫外线诱导的肿瘤在3或9个月大的动物中不进行性生长，但在15个月大的动物中开始进行性生长。我们研究了年轻和老年小鼠对一种这样的肿瘤6130的免疫反应，以确定这种免疫保护随年龄增长而崩溃的性质。在22个月大的动物中逐渐生长的6130肿瘤细胞仍然保留对针对高免疫原性“6130-A”抗原产生的细胞毒性T淋巴细胞（CTL）的敏感性，因此当移植到3个月和9个月大的动物中时仍然被免疫排斥，但在15个月大的小鼠中则没有。对CD 8（+）CTL应答的研究发现，在3-12月龄的动物中，可以在体内和体外产生对6130的原发性和继发性肿瘤特异性CTL应答。另一方面，在15月龄或更大的动物中观察到的对6130的CD 8（+）CTL应答显著降低或不存在。这些结果表明，抗原特异性CD 8（+）CTL的下降是老年动物对6130肿瘤生长易感性增加的主要原因。
A number of ultraviolet light-induced tumors that do not grow progressively in 3- or 9-month-old animals grow progressively in animals starting at similar to 15 months of age. We investigated the immune response to one such tumor, 6130, in young and old mice to determine the nature of this breakdown in immune protection with age. The 6130 tumor cells that grow progressively in 22-month-old animals still retain sensitivity to cytotoxic T lymphocytes (CTLs) generated against the highly immunogenic "6130-A'' antigen and consequently are still immunologically rejected when transplanted into 3- and 9-month-old animals, but not in mice older than 15 months. Investigation of the CD8(+) CTL response found that in animals 3-12 months old, primary and secondary tumor-specific CTL responses to 6130 can be generated in vivo and in vitro. On the other hand, the CD8(+) CTL responses to 6130 seen in animals 15 months of age or older were significantly depressed or absent. These results indicate that a decline in antigen-specific CD8(+) CTL is the major cause of increased susceptibility to 6130 tumor growth in older animals.