Journal of Experimental Medicine, Vol 180, 241-251, Copyright © 1994 by Rockefeller University Press

ARTICLES

Interleukin 2 receptor gamma chain expression on resting and activated lymphoid cells

T Nakarai, MJ Robertson, M Streuli, Z Wu, TL Ciardelli, KA Smith and J Ritz
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

The interleukin 2 receptor (IL-2R) is known to be comprised of at least three genetically distinct subunits termed alpha, beta, and gamma. These chains can be expressed individually or in various combinations resulting in distinct receptors with different affinities for IL-2. In contrast to alpha and beta, the cell surface expression of the gamma chain protein previously has not been well-characterized. To examine cell surface expression of IL-2R gamma on hematopoietic cells, we developed two new monoclonal antibodies (mAbs) specific for this protein. Both 1A11 (immunoglobulin [IgG1]) and 3G11 (IgM) specifically reacted with murine cells transfected with IL-2R gamma cDNA, and immunoprecipitation studies indicated that both antibodies precipitated a protein of approximately 62-65 kD. Scatchard analysis of IL-2 binding to murine cells transfected with cDNA-encoding combinations of IL-2R components demonstrated that neither beta nor gamma chain bind IL-2 with measurable affinity, but coexpression of both beta and gamma is sufficient to form an intermediate affinity receptor. In the absence of gamma chain, beta chain interacts with alpha chain to form a "pseudo- high" affinity receptor. In contrast, gamma chain does not appear capable of interacting with alpha in the absence of beta chain. Thus, gamma chain appears to interact only with beta, but beta chain is capable of interacting with both alpha and gamma. Using the newly developed mAbs to examine cell surface expression by immunofluorescence, resting T cells were found to express low levels of gamma chain without detectable alpha or beta. Early after mitogen stimulation, T cells expressed higher levels of alpha, beta, and gamma. However, at later time points, T cells expressed alpha and gamma in marked excess over beta. Thus, formation of high affinity IL-2R on activated T cells was primarily limited by beta chain expression. In contrast, resting natural killer (NK) cells constitutively expressed IL- 2R beta without detectable alpha or gamma. After activation with either IL-2 or IL-12, expression of both alpha and gamma transiently increased and then returned to very low levels. Expression of functional IL-2R on resting and activated NK cells, therefore, appeared to be primarily limited by the expression of gamma chain. IL-2 binding studies with resting NK cells confirmed the results of immunofluorescence studies indicating the presence of very low numbers of intermediate affinity (beta gamma) receptors for IL-2 on these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Zheng, C. F., Jones, G. J., Shi, M., Wiseman, J. C. D., Marr, K. J., Berenger, B. M., Huston, S. M., Gill, M. J., Krensky, A. M., Kubes, P., Mody, C. H. (2008). Late Expression of Granulysin by Microbicidal CD4+ T Cells Requires PI3K- and STAT5-Dependent Expression of IL-2R{beta} That Is Defective in HIV-Infected Patients. J. Immunol. 180: 7221-7229 [Abstract] [Full Text]  
• Engedal, N., Gjevik, T., Blomhoff, R., Blomhoff, H. K. (2006). All-trans Retinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3.. J. Immunol. 177: 2851-2861 [Abstract] [Full Text]  
• Gesbert, F., Moreau, J.-L., Theze, J. (2005). IL-2 Responsiveness of CD4 and CD8 lymphocytes: further investigations with human IL-2R{beta} transgenic mice. Int Immunol 17: 1093-1102 [Abstract] [Full Text]  
• Dang, N. H., Hagemeister, F. B., Pro, B., McLaughlin, P., Romaguera, J. E., Jones, D., Samuels, B., Samaniego, F., Younes, A., Wang, M., Goy, A., Rodriguez, M. A., Walker, P. L., Arredondo, Y., Tong, A. T., Fayad, L. (2004). Phase II Study of Denileukin Diftitox for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma. JCO 22: 4095-4102 [Abstract] [Full Text]  
• Geginat, J., Sallusto, F., Lanzavecchia, A. (2001). Cytokine-driven Proliferation and Differentiation of Human Naive, Central Memory, and Effector Memory CD4+ T Cells. J. Exp. Med. 194: 1711-1720 [Abstract] [Full Text]  
• O'Loughlin, E V, Pang, G P, Noltorp, R, Koina, C, Batey, R, Clancy, R (2001). Interleukin 2 modulates ion secretion and cell proliferation in cultured human small intestinal enterocytes. Gut 49: 636-643 [Abstract] [Full Text]  
• Dialynas, D. P., Shao, L.-e., Billman, G. F., Yu, J. (2001). Engraftment of Human T-Cell Acute Lymphoblastic Leukemia in Immunodeficient NOD/SCID Mice Which Have Been Preconditioned by Injection of Human Cord Blood. Stem Cells 19: 443-452 [Abstract] [Full Text]  
• Bani, L., Pasquier, V., Kryworuchko, M., Salamero, J., Theze, J. (2001). Unstimulated Human CD4 Lymphocytes Express a Cytoplasmic Immature Form of the Common Cytokine Receptor {{gamma}}-Chain. J. Immunol. 167: 344-349 [Abstract] [Full Text]  
• Monson, N. L., Fenske, T. J., Wei, S., Okragly, A. J., de Jong, J. L.O., Haak-Frendscho, M., O’Shea, J., Djeu, J., Sondel, P. M. (2001). A p74 common gamma receptor chain isoform facilitates IL-2 and IL-15 responses by the myelomonocytic cell line Tf-1{beta}2. J. Leukoc. Biol. 69: 419-425 [Abstract] [Full Text]  
• Olsen, E., Duvic, M., Frankel, A., Kim, Y., Martin, A., Vonderheid, E., Jegasothy, B., Wood, G., Gordon, M., Heald, P., Oseroff, A., Pinter-Brown, L., Bowen, G., Kuzel, T., Fivenson, D., Foss, F., Glode, M., Molina, A., Knobler, E., Stewart, S., Cooper, K., Stevens, S., Craig, F., Reuben, J., Bacha, P., Nichols, J. (2001). Pivotal Phase III Trial of Two Dose Levels of Denileukin Diftitox for the Treatment of Cutaneous T-Cell Lymphoma. JCO 19: 376-388 [Abstract] [Full Text]  
• Joshi, P. C., Zhou, X., Cuchens, M., Jones, Q. (2001). Prostaglandin E2 Suppressed IL-15-Mediated Human NK Cell Function Through Down-Regulation of Common {{gamma}}-Chain. J. Immunol. 166: 885-891 [Abstract] [Full Text]  
• Fehniger, T. A., Caligiuri, M. A. (2001). Interleukin 15: biology and relevance to human disease. Blood 97: 14-32 [Full Text]  
• Wang, K. S., Frank, D. A., Ritz, J. (2000). Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Blood 95: 3183-3190 [Abstract] [Full Text]  
• Suzuki, K., Nakajima, H., Saito, Y., Saito, T., Leonard, W. J., Iwamoto, I. (2000). Janus kinase 3 (Jak3) is essential for common cytokine receptor {gamma} chain ({gamma}c)-dependent signaling: comparative analysis of {gamma}c, Jak3, and {gamma}c and Jak3 double-deficient mice. Int Immunol 12: 123-132 [Abstract] [Full Text]  
• Rusterholz, C., Henrioud, P. C., Nabholz, M. (1999). Interleukin-2 (IL-2) Regulates the Accessibility of the IL-2-Responsive Enhancer in the IL-2 Receptor alpha  Gene to Transcription Factors. Mol. Cell. Biol. 19: 2681-2689 [Abstract] [Full Text]  
• Kolenko, V., Rayman, P., Roy, B., Cathcart, M. K., O'Shea, J., Tubbs, R., Rybicki, L., Bukowski, R., Finke, J. (1999). Downregulation of JAK3 Protein Levels in T Lymphocytes by Prostaglandin E2 and Other Cyclic Adenosine Monophosphate-Elevating Agents: Impact on Interleukin-2 Receptor Signaling Pathway. Blood 93: 2308-2318 [Abstract] [Full Text]  
• Castro, A., Sengupta, T. K., Ruiz, D. C., Yang, E., Ivashkiv, L. B. (1999). IL-4 Selectively Inhibits IL-2-Triggered Stat5 Activation, But Not Proliferation, in Human T Cells. J. Immunol. 162: 1261-1269 [Abstract] [Full Text]  
• Eicher, D. M., Waldmann, T. A. (1998). IL-2R{alpha} on One Cell Can Present IL-2 to IL-2R{beta}/{gamma}c on Another Cell to Augment IL-2 Signaling. J. Immunol. 161: 5430-5437 [Abstract] [Full Text]  
• Vanham, G. L., Penne, G., Vereecken, C., Vingerhoets, J., Kestens;, L., David, D., Bani, L., Moreau, J.-L., Theze, J. (1998). Interleukin-2 Receptor Subunit Expression and Function on Human Peripheral T Cells Is Not Dependent on the Anticoagulant. Blood 92: 2989-2993 [Full Text]  
• Raskin, N., Jakubowski, A., Sizing, I., Olson, D. L., Kalled, S. L., Hession, C. A., Benjamin, C. D., Baker, D. P., Burkly, L. C. (1998). Molecular Mapping with Functional Antibodies Localizes Critical Sites on the Human IL Receptor Common {gamma} ({gamma}c) Chain. J. Immunol. 161: 3474-3483 [Abstract] [Full Text]  
• David, D., Bani, L., Moreau, J.-L., Treilhou, M.-P., Nakarai, T., Joussemet, M., Ritz, J., Dupont, B., Pialoux, G., Theze, J. (1998). Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy. Proc. Natl. Acad. Sci. USA 95: 11348-11353 [Abstract] [Full Text]  
• David, D., Bani, L., Moreau, J.-L., Demaison, C., Sun, K., Salvucci, O., Nakarai, T., de Montalembert, M., Chouaib, S., Joussemet, M., Ritz, J., Theze, J. (1998). Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets. Blood 91: 165-172 [Abstract] [Full Text]  
• Meyer, W. K.-H., Reichenbach, P., Schindler, U., Soldaini, E., Nabholz, M. (1997). Interaction of STAT5 Dimers on Two Low Affinity Binding Sites Mediates Interleukin 2 (IL-2) Stimulation of IL-2 Receptor alpha  Gene Transcription. J. Biol. Chem. 272: 31821-31828 [Abstract] [Full Text]  
• Zambello, R., Facco, M., Trentin, L., Sancetta, R., Tassinari, C., Perin, A., Milani, A., Pizzolo, G., Rodeghiero, F., Agostini, C., Meazza, R., Ferrini, S., Semenzato, G. (1997). Interleukin-15 Triggers the Proliferation and Cytotoxicity of Granular Lymphocytes in Patients With Lymphoproliferative Disease of Granular Lymphocytes. Blood 89: 201-211 [Abstract] [Full Text]  
• Chang, D. Z., Wu, Z., Ciardelli, T. L. (1996). A Point Mutation in Interleukin-2 That Alters Ligand Internalization. J. Biol. Chem. 271: 13349-13355 [Abstract] [Full Text]  
• Wu, Z., Johnson, K. W., Goldstein, B., Choi, Y., Eaton, S. F., Laue, T. M., Ciardelli, T. L. (1995). Solution Assembly of a Soluble, Heteromeric, High Affinity Interleukin-2 Receptor Complex. J. Biol. Chem. 270: 16039-16044 [Abstract] [Full Text]  
• Wu, Z., Johnson, K. W., Choi, Y., Ciardelli, T. L. (1995). Ligand Binding Analysis of Soluble Interleukin-2 Receptor Complexes by Surface Plasmon Resonance. J. Biol. Chem. 270: 16045-16051 [Abstract] [Full Text]  
• Boussiotis, V., Barber, D., Nakarai, T, Freeman, G., Gribben, J., Bernstein, G., D'Andrea, A., Ritz, J, Nadler, L. (1994). Prevention of T cell anergy by signaling through the gamma c chain of the IL-2 receptor. Science 266: 1039-1042 [Abstract]  
• Russell, S., Johnston, J., Noguchi, M, Kawamura, M, Bacon, C., Friedmann, M, Berg, M, McVicar, D., Witthuhn, B., Silvennoinen, O, et, al. (1994). Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID. Science 266: 1042-1045 [Abstract]  
• Huang, L.-R., Chen, F.-L., Chen, Y.-T., Lin, Y.-M., Kung, J. T. (2000). Potent induction of long-term CD8+ T cell memory by short-term IL-4 exposure during T cell receptor stimulation. Proc. Natl. Acad. Sci. USA 97: 3406-3411 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS