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).