Augmentation of Murine Lymphokine‐activated Killer Cell Induction by a Factor Produced by Nocardia rubra Cell Wall Skeleton‐stimulated T Cells

Abstract

Four‐hour exposure of C3H/HeN mouse spleen cells to Nocardia rubra cell wall skeleton (N‐CWS) before 4‐day culture with a suboptimal dose of human recombinant interleukin 2 (rIL 2) augmented the induction of lymphokine‐activated killer (LAK) cell activity, whereas the treatment with N‐CWS alone induced no cytotoxicity. In accordance with this, the IL 2 binding activity of spleen cells was augmented by combined stimulation with N‐CWS and rIL 2. The augmented cytotoxicity was mediated by Thy‐1.2+, Lyt‐1.1−, Lyt‐2.1− and asialo GM1+ cells. Cell cultures in diffusion chambers revealed that N‐CWS‐treated spleen cells produced a LAK cell induction‐helper factor (LAK‐helper factor, LHF) when cultured with rIL 2. The LHF production required Thy‐1.2+, Lyt‐1.1+, Lyt‐2.1+ and asialo GM1− cells, and the coexistence of unstimulated accessory cells was also essential for the LHF production. Cells responding to both LHF and rIL 2 to generate LAK activity were Thy‐1.2−, Lyt‐1.1−, Lyt‐2.1− and asialo GM1+. The culture fluid of spleen cells stimulated with both N‐CWS and rIL 2 contained no tumor necrosis factor (TNF) activity, and the additional stimulation with N‐CWS caused no production of either IL 2 or interferon (IFN). Murine recombinant interleukin la (Mu‐rIL 1α) could not replace the augmentative effect of N‐CWS on LAK cell induction. These results suggest that in the presence of rIL 2, N‐CWS stimulates murine T cells to produce LHF that is probably distinct from IL 1, IL 2, TNF and IFN.