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

Abstract

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.