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Abstract

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.

Authors

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 1990 (13)

Title and authors Publication Year
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Dendritic cells stimulate primary human cytolytic lymphocyte responses in the absence of CD4+ helper T cells
JW Young, RM Steinman
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Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors
MA Caligiuri, A Zmuidzinas, TJ Manley, H Levine, KA Smith, J Ritz
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T-cell activation is required for efficient replication of human herpesvirus 6
N Frenkel, EC Schirmer, G Katsafanas, CH June
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Increased expression of the interleukin 2 (IL-2) receptor beta chain (p70) on CD56+ natural killer cells after in vivo IL-2 therapy: p70 expression does not alone predict the level of intermediate affinity IL-2 binding
SD Voss, RJ Robb, G Weil-Hillman, JA Hank, K Sugamura, M Tsudo, PM Sondel
Journal of Experimental Medicine 1990
Lymphokines and cytokines as cancer treatment.Immunotherapy realized
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Cancer 1990
Role of interleukin 2 receptor β chain in initiating anti-CD3 and interleukin 2-induced proliferation of human resting T cells
N Moiré, CF Calvo, D Métivier, JY Perrot, C Vaquero, M Hatakeyama, A Senik
European Journal of Immunology 1990
Interleukin-2 and the IL-2 Receptor: New Insight Into Structure and Function
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Journal of Investigative Dermatology 1990
Interleukin-2, anti-interleukin-2 receptor antibody, and activation of macrophages
M Belosevic, CA Nacy
Cellular Immunology 1990
Pro-interleukin-1β production by a subpopulation of human T cells, but not NK cells, in response to interleukin-2
RP Numerof, AN Kotik, CA Dinarello, JW Mier
Cellular Immunology 1990
Current Topics in Membranes and Transport
AI Tauber, AB Karnad, I Ginis
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Monoclonal antibodies against interleukin-2 receptors in the immunosuppressive management of kidney graft recipients
BL Mauff, D Cantarovich, Y Jacques, JP Soulillou
Transplantation Reviews 1990
The Molecular Aspects of Autoimmunity
DW Ballard, MR Fung, E Böhnlein, WC Greene
The Molecular Aspects of Autoimmunity 1990

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