Interleukin-12 induced cytolytic activity in lymphocytes from recipients of autologous and allogeneic stem cell transplants

Interleukin-12 (IL-12) has been reported to enhance the cytolytic activity of NK and activated T cells and to induce low levels of lymphokine-activated killer (LAK) activity in normal human lymphocytes. Therapy with IL-12 has induced tumor eradication in murine models. These observations suggest that IL-12 might have a role as treatment for minimal residual disease following transplantation. To determine whether PBL from recipients of autologous (autoSCT) and allogeneic (alloSCT) bone marrow or peripheral blood stem cell transplants respond to IL-12 with generation of LAK activity, PBL were incubated with IL-12 for 5 days, then tested in a 51Cr release assay for lysis of Daudi. PBL from 17 normal 'control' individuals were similarly tested and lysis was observed in only 3/17 (mean 16.9% of the three). By contrast, PBL from 10/12 patients obtained a median of 30 days after autoSCT, exhibited significant IL-12-induced LAK activity (mean lysis, 35.3%, P < 0.005 vs controls). PBL from 18 of 20 patients tested a median of 44 days after alloSCT also exhibited significant LAK activity (mean lysis, 30.0%, P < 0.005 vs controls). In autoSCT recipients, IL-12 and IL-2 at high concentrations (1000 U/ml each) were additive for induction of LAK activity, whereas low, suboptimal concentration of IL-12 (250 U/ml) and IL-2 (1 U/ml) were synergistic in 3/5 experiments. The percentage of PBL expressing IL-12 receptor beta 1 chain (IL-12r beta 1) was higher in stem cell recipients than in normal individuals, P < 0.05. Moreover, a higher percentage of IL-12r beta 1-positive PBL was associated with greater IL-12-induced LAK activity in transplant recipients. These studies demonstrate that PBL obtained early after stem cell transplantation have a higher percentage of cells expressing IL-12r beta 1 and respond to IL-12 with significantly greater LAK cytotoxicity than PBL from normal controls. These results suggest that IL-12 is a potentially attractive candidate for study as consolidative immunotherapy after stem cell transplantation.