Antitumor activity of a Streptococcus pyogenes preparation (OK-432). II. Analysis of the cytotoxic lymphocytes induced by OK-432 injection into tumor-bearing F344 rats.
In the present study, the antigenic phenotype and target cell specificity of the cytotoxic lymphocytes observed in F344 rats following the ip inoculation of a syngeneic MADB106 mammary carcinoma and the single injection of OK-432 were examined. When the cytotoxicity of peritoneal exudate cells (PECs) was measured in a 4-hour 51Cr release assay, appreciable cytotoxicity against MADB106 tumor cells was evident by day 7-14 following OK-432 injection. With the use of an antibody (R1-3B3) and complement depletion of cytotoxic PECs, the MADB106 killer cells appeared to consist of both R1-3B3- (non-T) and R1-3B3+ (T) cells, with most of the anti-MADB106 killing residing in the R1-3B3- cell population. The R1-3B3- killer cells were further defined as: a) phenotypically asialoGM1+, b) present in athymic nude rats, and c) accompanied by some augmentation of YAC-1 killing [the prototype rat natural killer (NK) target], suggesting that some of these R1-3B3- killer cells were typical NK cells. However, it was also observed that most of the R1-3B3- cells that killed MADB106 tumor cells were: 1) phenotypically or functionally different from either cytotoxic T-cells or typical NK cells; 2) observed only in MADB106 tumor-bearing rats challenged with OK-432; 3) not present on day 1-2 following OK-432 injection, the time when YAC-1 killing was maximally augmented; and 4) present in high numbers in a secondary response following reinoculation of the MADB106 tumor cells into cured rats. The in vivo relevance and possible derivation of these various cytotoxic lymphocyte populations in the syngeneic tumor-bearing hosts are discussed.
D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D002448:Cell Adhesion; D002470:Cell Survival / Q000187:drug effects; D007694:Killer Cells, Natural / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D010844:Picibanil / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D001688:Biological Products; D010844:Picibanil