Regulation of large granular lymphocytes and human T cell growth and function by recombinant interleukin 2. II. Acquisition of potent cytotoxic capabilities.
Human large granular lymphocytes (LGL) and T cells were separated from peripheral blood on discontinuous density gradients of Percoll. On a per cell basis, cultured LGL demonstrated higher levels of cytotoxicity against K562 cells than fresh LGL. Cultured T cells acquired cytotoxicity against K562 cells, although they were less cytotoxic than fresh or cultured LGL. During culture, these LGL retained the 3G8, NKH1, OKM1, and OKT10 antigens. Cultured T cells retained the T101 antigen and acquired the OKM1 and OKT10 antigens, but remained negative for the 3G8 or NKH1 antigens. A series of pharmacologic agents known to inhibit cytotoxicity of fresh LGL were also tested for their effects on cultured LGL and T cells. Ethylenediaminetetraacetic acid, known to inhibit the binding of effectors to target cells, inhibited the cytotoxicity of cultured LGL and T cells to the same degree that it inhibited the cytotoxicity of fresh LGL. In contrast, agents which primarily effect post-binding events in cytotoxicity (trypsin, D-mannose 6-P, dexamethasone, prostaglandin E2, anti-LGL granule antibody, and 9.1C3 monoclonal antibody) inhibited the cytotoxicity of cultured LGL and T cells to a much lesser extent than fresh LGL. In addition, on the basis of Michaelis-Menten's kinetic analysis, cultured LGL and T cells developed a higher binding affinity to K562 cells than fresh LGL.
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015232:Dinoprostone; D006801:Humans; D007376:Interleukin-2; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008358:Mannose / Q000494:pharmacology; D010641:Phenotype; D011458:Prostaglandins E / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014357:Trypsin / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014357:Trypsin; D015232:Dinoprostone; D008358:Mannose