Induction of NK activity in large granular lymphocyte leukemia: activation with anti-CD3 monoclonal antibody and interleukin 2.
Large granular lymphocyte (LGL) leukemia is a rare disease characterized by clonal expansion of LGL associated with chronic neutropenia, multiple auto-antibodies, and occasionally polyarthritis. We studied cell surface antigen expression and functional activity of leukemic LGL from ten such patients. Using two-color flow cytometric analysis, we found that leukemic LGL from all ten patients expressed the CD3 and HNK-1 markers, while cells from only four patients expressed IgG Fc receptors (FcR). The LGL leukemic cells had little or no NK activity (defined as MHC-nonrestricted cytotoxicity against K562 target cells); however, NK activity could be induced in leukemic LGL by in vitro treatment with as little as 0.05 microgram/mL of anti-CD3 monoclonal antibody. Cell sorting experiments demonstrated that NK activity was induced in CD3+ leukemic LGL (either CD3+, HNK-1+ or CD3+, FcR+) with anti-CD3 monoclonal antibody but not in normal CD3+, FcR- T cells. Treatment with purified interleukin 2 (IL 2) also caused direct activation of some CD3+ leukemic LGL. Despite induction with anti-CD3 MAb or IL 2, activated leukemic LGL did not proliferate or express high density IL 2 receptors detectable by cell sorter analysis. Treatment with alpha interferon had minimal effect on NK activity of LGL leukemic cells. These results suggest that leukemic LGL may provide a useful model for examining the signals required for LGL maturation and activation.
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000473:pathology*; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007370:Interferon Type I; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2