Costimulation of human natural killer cell proliferation: role of accessory cytokines and cell contact-dependent signals.

摘要: Abstract Despite the importance of natural killer (NK) cells in immune response, regulation human NK cell growth has not been well characterized. We have hypothesized that, similar to proliferation T and B lymphocytes, optimal requires costimulatory signals as a primary mitogenic stimulus. Evidence for costimulation by both soluble cytokines contact-dependent factors is presented. Soluble IL-1 TNF were found augment response cytokines, including IL-2, IL-4, IL-7, IL-12. The effect strongly enhanced calcium ionophore ionomycin. Coculture with irradiated K562 can largely substitute signal provided Costimulation intimate contact reconstituted cell-free supernatants. Activated lymphocytes also mediate cells; resting PBMC, several NK-sensitive lines, all NK-resistant lines tested be costimulatory. Engagement CD16 did proliferation. Thus, triggering killing or antibody-dependent cell-mediated cytotoxicity (ADCC) does consistently provide Cell appear involve known receptors that costimulate cells, CD2, CD27, CD28, CD29, LFA-1. molecular nature putative receptor remains elucidated. Nevertheless, could expanded vitro using leukocyte-conditioned medium (LCM) source IL-2 accessory ionomycin bypass costimulation. LCM express typical antigens ADCC. Further characterization may elucidate physiologic ultimately allow more effective manipulation these immunotherapy diseases.