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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
Author(s) -
Yamada Sachihiro,
Ruscetti Francis W.,
Overton W. Roy,
Herberman Ronald B.,
BirchenallSparks Maria C.,
Ortaldo John R.
Publication year - 1987
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.41.6.505
Subject(s) - biology , interleukin 2 , cytotoxicity , microbiology and biotechnology , recombinant dna , function (biology) , interleukin , receptor , immunology , lymphocyte , interleukin 15 , cell growth , interleukin 4 , cytokine , in vitro , gene , biochemistry
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 [ 125 l]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.