Synergistic effect of Nocardia rubra cell wall skeleton and recombinant interleukin 2 for in vivo induction of lymphokine-activated killer cells.
C57BL/6 mice inoculated i.p. with 3LL tumor cells were treated by local combination therapy with Nocardia rubra cell wall skeleton (N-CWS) and recombinant interleukin 2 (rIL-2). The combination treatment significantly prolonged their survival and augmented lymphokine-activated killer (LAK) activity of peritoneal cavity lymphocytes (PCL), compared with treatments with rIL-2 alone or N-CWS alone. After in vitro culture of peritoneal exudate mononuclear cells with rIL-2, the nonadherent population derived from N-CWS-injected tumor-bearing mice showed a significantly higher LAK activity than did that population derived from saline solution-injected mice. When N-CWS-induced PCL were cocultured with either N-CWS-induced macrophages or control macrophages in the presence of rIL-2, their LAK activity was higher than that of control PCL. Therefore, it was suggested that N-CWS-induced PCL themselves have a more potent ability as precursors of LAK cells. Phenotypic analysis on PCL populations revealed that N-CWS-induced PCL contained increased proportions of CD3+CD4-CD8- cells and asialo GM-1+ cells compared with control PCL. These results suggest that N-CWS selectively accumulates potent LAK precursors, namely, CD3+CD4-CD8- T-cells and asialo GM-1+ natural killer cells, at the injection site and that LAK cells are efficiently induced by subsequent administration of rIL-2.
Miyazaki
K
K
Second Department of Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yasumoto
K
K
Yano
T
T
Matsuzaki
G
G
Sugimachi
K
K
Nomoto
K
K
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000494:pharmacology*; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003599:Cytoskeleton / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D016130:Immunophenotyping; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009615:Nocardia; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D001427:Bacterial Toxins; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins