rIL-2-activated killer cell generation is influenced by autologous TNF-alpha production.
Low-density (LD) lymphocytes and their CD16+ and CD16- subsets were cultured with recombinant interleukin-2 (rIL-2) in the presence or absence of tumor necrosis factor-alpha (TNF-alpha)-neutralizing antibodies (Abs). Cultures were evaluated with respect to the cell recovery, K562 cytolytic potential and interferon (IFN)-gamma production. The addition of anti-TNF-alpha neutralizing Abs to rIL-2-activated cultures of LD lymphocytes resulted in greater cell expansion and a decrease in cytolytic potential. In the CD16+ subpopulation of LD lymphocytes, there was an increase in cytolytic potential and no improvement in the cell yield was observed. The CD16- subpopulation of LD lymphocytes was not affected by the Abs. In cultures with anti-TNF alpha Abs (polyclonal or monoclonal), a decrease in the rIL-2-dependent generation of IFN-gamma was observed. Recombinant TNF-alpha, when added to rIL-2-supplemented cultures of LD lymphocytes, enhanced the rIL-2-induced generation of IFN-gamma in a dose-dependent manner. TNF-alpha appeared to up-regulate rIL-2-induced IFN-gamma production by LD lymphocytes and to modulate lymphokine-activated killer cell generation (neutralization of TNF-alpha promoted cell expansion in LD lymphocyte cultures and cytotoxicity in CD16+ lymphocyte cultures).
Lange
A
A
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.
Moniewska
A
A
Fetting
R
R
Ernst
M
M
Flad
H D
HD
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D007376:Interleukin-2 / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D009500:Neutralization Tests; D017452:Receptors, IgG / Q000032:analysis; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma