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American Journal of Pathology, Vol 140, 233-242, Copyright © 1992 by American Society for Investigative Pathology

REGULAR ARTICLES

Cytolytic T lymphocytes and antibodies to myocytes in adriamycin- treated BALB/c mice. Evidence for immunity to drug-induced antigens

SA Huber and A Moraska
Department of Pathology, University of Vermont, Burlington 05405.

Female BALB/c mice were given a single intravenous injection of between 0.1 and 10 mg adriamycin/kg body weight and were killed between 2 and 16 days later. Natural killer (NK) cell activity in the spleen was measured using YAC cell targets. Natural killer cell activity was slightly elevated 2 to 5 days after drug injection and significantly depressed by day 9 compared with spleen cells from untreated animals. Adriamycin-treated mice developed both cytolytic T lymphocytes (CTL) and antibodies to drug-treated myocytes. Peak CTL response occurred between days 9 and 13, whereas antibody reactivity continued to increase throughout the observation period. The effector cell belonged to the CD8+ T lymphocyte subpopulation, because cytolytic activity could be reduced by treating the cells with anti-Lyt 2 antibody and complement, whereas anti-L3T4 (CD4+ cell-specific) treatment either had no effect or increased cytotoxicity. Both CTL and antibody reactivity could be absorbed with adriamycin-treated myocyte monolayers but not by non-drug-treated myocytes. Furthermore CTL reactivity could be only partly removed by adriamycin-treated skin fibroblasts. Adriamycin concentrations in the heart were measured by flourometry and demonstrated only a gradual decrease in the drug over the 16-day period. Immunofluorescent staining of myocardial sections demonstrated increased numbers of both T lymphocytes and macrophages in the hearts of adriamycin-treated mice compared with untreated controls.




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Copyright © 1992 by the American Society for Investigative Pathology.