Persistence of the immunoprotective effects of leukemia × fibroblast hybrid cells toward leukemia in histocompatible mice

Abstract

Hybrids of ASL-1 murine leukemia cells and LM(TK-) cells, a cultured line of mouse fibroblast origin, stimulate partial immunity toward ASL-1 cells in ( A J × C3H HeJ ) F 1 mice ( F 1 mice). Such mice ordinarily exhibit no resistance to the malignant proliferation of ASL-1 cells. Unprotected animals invariably die within 14–18 days after receiving as few as 200 ASL-1 cells. The hybrid cells, the mice used in the experimental studies and the leukemia cells used for challenge all share the same histocompatibility antigens. ASL-1 cells are H-2 a; LM(TK-) cells are H-2 k, both ASL-1 × LM(TK-) hybrid cells and A J × C3H HeJ ) F 1 mice are H-2 a/k. The long-term persistence of the immunoprotective properties of the hybrid cells toward murine leukemia was investigated by using cells that had been in continuous culture for approx. 36 months. ( A J × C3H HeJ ) F 1 mice injected previously with hybrid cells in continuous culture and then challenged with up to 10 7 ASL-1 cells survived longer ( p < 0.001) than mice who had not received hybrid cells previously. Some mice challenged with lesser number of ASL-1 cells survived indefinitely (> 200 days). The median survival time of F 1 mice injected simultaneously with 10 7 hybrid cells and 200 or 2000 ASL-1 cells was significantly ( p < 0.001) prolonged as well, although the differences between experimental and control groups are less pronounced than if the hybrid cells were injected before challenge with ASL-1 cells. The hybrid cells like those freshly prepared continue to be rejected by histocompatible precipients. In no instance has there been evidence of a progressively growing tumor of hybrid cells in immunocompetent F 1 mice. Hybrid cells like those investigated previously do form rapidly growing metastasizing tumors in immunodeficient nu/nu (BALB/c) or X-irradiated (550 R) F 1 mice. The cells possess approx. 70 chromosomes (reduced from 85) including chromosomes identified as having originated in each parental source. Like ( A J × C3H HeJ ) F 1 animals, they continue to express both H-2 a and H-2 k antigenic determinants.