Flood P M, Liu X, Alexander R, Schreiber H, Haque S
Department of Periodontics, University of North Carolina Schools of Medicine and Dentistry, Chapel Hill 27599-7455, USA.
J Immunother. 1998 Jul;21(4):307-16. doi: 10.1097/00002371-199807000-00008.
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 approximately 15 months of age. We investigated the immune response to one such tumor, 6130, in young and old mice to determine in nature of this breakdown in immune protection with age. The 6130 tumor cells that grow progressively in 22-month-old animals still retain sensitivity of 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.
一些在3个月或9个月大的动物中不会渐进性生长的紫外线诱导肿瘤,在大约15个月大的动物中会渐进性生长。我们研究了年轻和年老小鼠对一种这样的肿瘤6130的免疫反应,以确定这种随年龄增长的免疫保护破坏的本质。在22个月大的动物中渐进性生长的6130肿瘤细胞,仍然保留对针对高度免疫原性的“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会被免疫排斥,但在15个月以上的小鼠中则不会。对CD8 + CTL反应的研究发现,在3至12个月大的动物中,对6130的原发性和继发性肿瘤特异性CTL反应可以在体内和体外产生。另一方面,在15个月及以上的动物中看到的对6130的CD8 + CTL反应明显降低或不存在。这些结果表明,抗原特异性CD8 + 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。