Differentiation of NK-like cells from OKT3-, OKT11+, and OKM1+ small resting lymphocytes by culture with autologous T cell blasts and lymphokine.
NK-like cells have been generated in vitro from a resting lymphocyte population of PBMC by 8 days culture with mitomycin C-treated autologous T cell blasts and lymphokine. The responder lymphocyte population was purified to the extent that it lacked classical NK cells, and lacked the precursors of MLC-derived NK-like cells and of lymphokine-activated killer cells. The NK-like cells were not generated when the responder lymphocytes were cultured with either T cell blasts or lymphokine alone. Thus, at least two signals are required for their activation. Metabolically inactive T cell blasts plus lymphokine were effective in stimulating the generation of NK-like cells, suggesting that a membrane determinant on the T cell blasts was involved in activation. The phenotype of the NK-like cells and their precursors was analyzed by monoclonal antibody and complement treatment. The phenotype of both precursor and effector cells was OKT3-, OKT11+, and OKM1+, with a distinct pattern of reactivity with OKT8 and Leu-7 for each individual donor tested. The NK-like cells were morphologically large granular lymphocytes, and they killed a variety of target cells. These studies show that signals provided by autologous T cell blasts and lymphokine are essential in triggering the differentiation of NK-like cells from appropriately purified resting lymphocytes. This mechanism of activation could occur in vivo, leading to the generation of NK cells subsequent to an antigen-specific T cell response.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D002454:Cell Differentiation; D003470:Culture Media; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007399:Interphase; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D003470:Culture Media; D008222:Lymphokines