The therapeutic significance of concomitant antitumor immunity. II. Passive transfer of concomitant immunity with Ly-1+2- T cells primes established tumors in T cell-deficient recipients for endotoxin-induced regression.
Intravenous injection of 50 micrograms bacterial endotoxin can cause complete regression of an established SA1 sarcoma, but not if the tumor ir growing in mice that are incapable of generating concomitant immunity because they have been made T cell-deficient by thymectomy and gamma-radiation (TXB mice). It also was shown that endotoxin fails to cause complete regression of a tumor that is either too large or too small. Only when administered on day 9 of tumor growth, at the time of peak concomitant immunity, did endotoxin cause the tumor to undergo complete regression. Direct evidence that the antitumor effect of endotoxin is dependent on concomitant immunity consisted in the demonstration that an SA1 sarcoma growing in TXB recipients can be primed for endotoxin-induced regression by IV infusion of splenic T cells from concomitantly immune donors bearing an endotoxin-susceptible 9-day tumor. Surprisingly, the donor T cells that primed the recipient tumor for endotoxin-induced regression were of the Ly-1+2- phenotype, as evidenced by their susceptibility to treatment with anti-Ly-1 antibody and complement, and their complete resistance to treatment with anti-Ly-2 antibody and complement. They were different, therefore, from the T cells that cause the regression of smaller tumors in gamma-irradiated recipients without the aid of endotoxin. It is suggested that the antitumor function of endotoxin depends on its ability to cause intratumor macrophages to acquire and express tumoricidal function, but only after the macrophages have been activated by Ly-1+2-tumor-sensitized T cells.
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004731:Endotoxins / Q000008:administration & dosage*; D007116:Immunization, Passive; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D012477:Salmonella enteritidis / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D000950:Antigens, Ly; D004731:Endotoxins