LOSS OF RESISTANCE TO A HIGHLY IMMUNOGENIC TUMOR WITH AGE CORRESPONDSTO THE DECLINE OF CD8 T-CELL ACTIVITY

A number of ultraviolet light-induced tumors that do not grow progress ively in 3- or 9-month-old animals grow progressively in animals start ing at similar to 15 months of age. We investigated the immune respons e to one such tumor, 6130, in young and old mice to determine the natu re of this breakdown in immune protection with age. The 6130 tumor cel ls that grow progressively in 22-month-old animals still retain sensit ivity to cytotoxic T lymphocytes (CTLs) generated against the highly i mmunogenic ''6130-A'' antigen and consequently are still immunological ly rejected when transplanted into 3- and 9-month-old animals, but not in mice older than 15 months. Investigation of the CD8(+) CTL respons e found that in animals 3-12 months old, primary and secondary tumor-s pecific CTL responses to 6130 can be generated in vivo and in vitro. O n the other hand, the CD8(+) CTL responses to 6130 seen in animals 15 months of age or older were significantly depressed or absent. These r esults indicate that a decline in antigen-specific CD8(+) CTL is the m ajor cause of increased susceptibility to 6130 tumor growth in older a nimals.