Open AccessInduction Mechanism of Human Blood CD8 + T Cell Proliferation and Cytotoxicity by Natural Killer Cell Stimulatory Factor (Interleukin‐12)
Author(s) -
Nabioullin Roustem,
Sone Saburo,
Nil Akihiko,
Haku Takashi,
Ogura Takeshi
Publication year - 1994
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1994.tb02958.x
Subject(s) - cytotoxic t cell , cd8 , cytokine , biology , natural killer cell , lymphokine activated killer cell , tumor necrosis factor alpha , monocyte , microbiology and biotechnology , interferon gamma , cytotoxicity , interleukin 12 , immunology , chemistry , immune system , biochemistry , in vitro
Natural killer cell stimulatory factor (NKSF J 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 51 Cr 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.