Induction mechanism of human blood CD8+ T cell proliferation and cytotoxicity by natural killer cell stimulatory factor (interleukin-12).
Natural killer cell stimulatory factor (NKSF/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 by 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 gamma (IFN gamma) 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 IFN gamma, but not of antibody against tumor necrosis factor alpha. Induction of NKSF-inducible cytotoxic CD8+ cells was inhibited by addition of transforming growth factor beta, 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.
Nabioullin
R
R
Third Department of Internal Medicine, University of Tokushima School of Medicine.
Sone
S
S
Nii
A
A
Haku
T
T
Ogura
T
T
D002051:Burkitt Lymphoma; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018288:Carcinoma, Small Cell; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008175:Lung Neoplasms; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006133:Growth Substances; D007376:Interleukin-2; D011994:Recombinant Proteins; D018664:Interleukin-12