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Synergistic Effect of Nocardia rubra Cell Wall Skeleton and Recombinant Interleukin 2 for in Vivo Induction of Lymphokine-activated Killer Cells

Second Department of Surgery, Faculty of Medicine [K. M., K. Y., T. Y., K. S.], and Department of Immunology, Medical Institute of Bioregulation [G. M., K. N.], Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812, Japan

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.

¹ To whom requests for reprints should be addressed.

² Present address: Matsuyama Red Cross Hospital, Bunkyo-Cho 1, Matsuyama 790, Japan.

Received 11/ 9/90. Accepted 7/18/91.