Induction mechanism of human blood CD8+ T cell proliferation and cytotoxicity by natural killer cell stimulatory factor (interleukin-12).

Abstract

Natural killer cell stimulatory factor (NKSFJ IL‐12) has been found to induce cytotoxic activity of human blood T cells. In the present study, the effect of NKSF on induction of cytotoxic CD8+ T cells in the presence or absence of monocytes was examined. Highly purified lymphocytes (>99%) and monocytes (>90%) were isolated hy centrifugal elutriation from peripheral blood of normal donors. Then, CD8+ cells were isolated with antibody‐bound magnetic beads from purified lymphocytes. The cytotoxicity of CD8+ cells was measured by 51Cr release assay for 4 h. NKSF enhanced the proliferative response of CD8+ cells stimulated with suboptimal concentrations of interleukin‐2 (IL‐2), but rather inhibited their proliferative and cytotoxic responses on stimulation with an optimal concentration of IL‐2. NKSF stimulated CD8+ cells to produce interferon 7 (IFNγ) irrespective of the presence of added IL‐2, and this effect was augmented by co‐cultivation with monocytes. Blood monocytes upregulated induction of cytotoxic CD8+ cells stimulated with NKSF alone, and this effect was abolished by addition of antibody against IFNγ, but not of antibody against tumor necrosis factor a. Induction of NKSF‐inducible cytotoxic CD8+ cells was inhibited by addition of transforming growth factor β, but not of IL‐4. These observations suggest that in situ induction of NKSF‐stimulated cytotoxic CD8+ cells may be regulated by complex cytokine networks, depending on the participation of monocytes.