Age-related changes of natural antitumor resistance in spontaneously hypertensive rats with T-cell depression.
We investigated the relationship between age-related changes in natural resistance and antitumor effects using a spontaneously hypertensive rat (SHR rat) strain which shows a progressive decline of the number of T-cells and their functions as a result of aging. The growth of a weakly antigenic mammary adenocarcinoma SST-2 was significantly suppressed in SHR rats ages 2 and 3 months, whereas in SHR rats ages 1 or 8 months no suppression of the tumor growth was observed. Splenic natural killer cell activity among the SHR rats was still low at 1 month, when the T-cell function is relatively intact; it reached a maximum level at 3 months and thereafter rapidly decreased. On the other hand, the cytostatic activity of peritoneal macrophages, which is also low at 1 month and becomes high at 3 months, thereafter remained at high levels until 8 months of age. That is, the kinetics of natural killer cell activity during the aging processes runs parallel to the function of suppressing tumor growth. Treatment with anti-asialomonoganglioside antiserum abrogated the suppressive activity of SST-2 tumor growth in 3-month-old SHR rats. Treatment with double stranded RNA polyinosinate-polycytidylate, an interferon inducer, produced significant suppression of the tumor growth in SHR rats ages 3 and 8 months. These results suggest that the participation of natural killer cells is a principal effector mechanism in the suppression of SST-2 tumor growth in SHR rats ages 2 and 3 months.
D000375:Aging; D000818:Animals; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D011070:Poly I-C