Mechanism of natural delayed-type hypersensitivity reactions to tumor cells in nonimmunized syngeneic guinea pigs.
Nonimmunized 2/N guinea pigs respond to the presence of chemical carcinogen-transformed syngeneic tumorigenic cells with a sustained (delayed-hypersensitivity-type) 4-day intradermal induration consisting of predominantly polymorphonuclear leukocytes on day 1 and mononuclear cells by day 4, which is independent of the presence of tumor-specific antigens on the tumorigenic cells. Chemical carcinogen-induced morphologically transformed but nontumorigenic cells also induce a polymorphonuclear response by day 1, but neither induration nor a mononuclear response is present on day 4, demonstrating the specificity of the 4-day sustained indurative response for tumorigenic cells. Induration and cellular infiltrates are unaltered if tumor cells are treated prior to injection with the cytostatic lymphokine lymphotoxin or with x-irradiation to inhibit cell proliferation. The intradermal polymorphonuclear leukocyte host response on day 1, but not the mononuclear response on day 4, is also induced by mitomycin C-treated cells or a cytokine culture medium from the cells. No response is present on day 1 or day 4 when cell membranes or lyophilized cells are injected. Thus natural delayed-hypersensitivity-type skin reactivity is a mononuclear leukocyte response specifically directed against intact and metabolically active but not necessarily proliferating tumor cells.
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005354:Fibrosarcoma / Q000276:immunology*; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D007428:Intradermal Tests; D008214:Lymphocytes / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000473:pathology
D000951:Antigens, Neoplasm; D008233:Lymphotoxin-alpha