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A novel IL-2 receptor, distinct from the Tac protein, has been identified on the surface of purified human natural killer (NK) cells by chemical cross-linking of 125I-IL-2. This protein is approximately 70,000 D in size (p70) and appears to be identical to the recently recognized second subunit of the human high affinity IL-2 receptor complex. Scatchard analysis of 125I-IL-2 binding to purified NK cells revealed approximately 2,300 p70 binding sites per cell with an apparent dissociation constant of 200 pM, a value intermediate between the previously recognized high and low affinity forms of the human IL-2 receptor. The monoclonal anti-Tac antibody did not inhibit the cross-linking of 125I-IL-2 to the p70 binding sites present on NK cells. Functionally, the addition of high concentrations of recombinant IL-2 to the enriched NK cells promoted a rapid augmentation of cytolytic activity and a more delayed increase in cellular proliferation. Anti-Tac effectively blocked the IL-2-induced proliferative response in these cells, but failed to alter the enhancement of cytotoxicity. Analysis of NK cytoplasmic RNA isolated at various time points after IL-2 stimulation revealed the rapid induction of c-myb and Tac gene expression that was also not inhibited by the anti-Tac antibody. These findings suggest that IL-2 binding to the p70 receptor constitutively expressed on the surface of NK cells may mediate both the development of increased cytolytic activity and rapid changes in gene expression. The activation of the Tac gene may in turn permit the formation of the high affinity IL-2 receptor complex (comprised of at least the Tac and p70 proteins) that appears to transduce the requisite signals involved in NK cell proliferation.


J H Kehrl, M Dukovich, G Whalen, P Katz, A S Fauci, W C Greene


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Citations to this article in year 1989 (8)

Title and authors Publication Year
The cellular immunotherapy of cancer: Current and potential uses of interleukin-2
PM Sondel, JA Hank, PC Kohler, JA Sosman, G Weil-Hillman, P Fisch, FH Bach
Critical Reviews in Oncology/Hematology 1989
The control of antibody production by immunomodulatory molecules
PE Lipsky
Arthritis & Rheumatism 1989
Interactions between receptors for interleukin 2 and interleukin 4 on lines of helper T cells (HT-2) and B lymphoma cells (BCL1)
R Fernandez-Botran, VM Sanders, ES Vitetta
Journal of Experimental Medicine 1989
Interleukin-2 can induce suppression of human natural killer cell cytotoxicity
K Hellstrand, S Hermodsson
Clinical & Experimental Immunology 1989
Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes
M Kobayashi, L Fitz, M Ryan, RM Hewick, SC Clark, S Chan, R Loudon, F Sherman, B Perussia, G Trinchieri
Journal of Experimental Medicine 1989
Advances in Immunology
ML Thoman, WO Weigle
Advances in immunology 1989
Decreased expression of interleukin-2 binding molecules (p70/75) in T cells from patients with systemic lupus erythematosus
T Tanaka, O Saiki, S Negoro, T Igarashi, T Kuritani, H Hara, M Suemura, S Kishimoto
Arthritis & Rheumatism 1989
Human Pulmonary Natural Killer (NK) Cells Exhibit Limited Lymphokine-activated Killer (LAK) Activity
WC Yarbrough, JC Weissler
American journal of respiratory cell and molecular biology 1989