Loss of resistance to a highly immunogenic tumor with age corresponds to the decline of CD8 T cell activity.

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 ∼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.