Regulation of human large granular lymphocyte and T cell growth and function by recombinant interleukin 2: induction of interleukin 2 receptor and promotion of growth of cells with enhanced cytotoxicity.
Human large granular lymphocytes (LGL), which account for virtually all natural killer activity, and T cells were separated from low and high density fractions of Percoll gradients, respectively. We were unable to detect interleukin 2 receptors (IL 2R) on fresh LGL and T cells using flow cytometric analysis with anti-Tac monoclonal antibody or radiolabeled probes with [125I]anti-Tac. IL 2R messenger ribonucleic acid was not observed in fresh LGL or T cells. Although phytohemagglutinin induced the expression of IL 2R on purified LGL and T cells, recombinant IL 2 (rIL 2) alone induced IL 2R messenger ribonucleic acid, IL 2R, and proliferation of LGL but not of T cells. The high level of cytotoxicity of cultured LGL against K562 cells was directly dependent on rIL 2. When T cells were costimulated by phytohemagglutinin and rIL 2 for 3 days, only very low levels of cytotoxicity were generated. Proliferation and cytotoxicity against K562 cells inhibited the culture of LGL in the presence of anti-Tac antibody for 3 days. LGL began to grow more rapidly after 5 days in culture with rIL 2 alone. When rIL 2 were removed from growing LGL for 1 day, proliferation completely stopped, and cytotoxicity was no longer detected. These data indicate that rIL 2 induces IL 2R expression in fresh LGL at the transcriptional level, promoting growth and enhancing cytotoxicity. More importantly, the presence of rIL 2 is necessary and sufficient to induce proliferation of resting LGL and to maintain the growth of LGL with potent lytic activity.
D002455:Cell Division; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D013997:Time Factors
D006684:HLA-DR Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins