Receptor for Interleukin 13

Abstract

Interleukin 13 (IL-13) shares many biological properties with IL-4, and although the receptor for IL-4 (IL-4R) has been characterized, the expression and structure of IL-13 receptor are unknown. We report here that human renal cell carcinoma (RCC) cells express large numbers of functional IL-13R. Human B lymphocytes and monocytes expressed a very small number of IL-13R, while resting or activated human T cells expressed little or no IL-13R. IL-4 did not compete for IL-13 binding, while IL-13 competed for IL-4 binding, even though IL-4R and IL-13R are structurally distinct on human RCC cells. IL-13 cross-linked with one major protein that is similar in size to the γcsubunit of IL-2, −4, −7, −9, and −15 receptors but was not recognized by anti-γcor anti-IL-4R antibodies. IL-4, on the other hand, cross-linked with two major proteins, the smaller of which appears to be similar in size to IL-13R and γc, but (like the IL-13R) it did not react with anti-γcantibody. Although as shown in this study and in previous studies, γcis a functional component of IL-4R in lymphoid cells, it does not appear to be associated with IL-4R on RCC cells. Even in the absence of common γ chain IL-4 and IL-13 were able to up-regulate intracellular adhesion molecule-1 antigen on RCC cells. These data suggest that the interaction of IL-13 with IL-4R does not involve γcand IL-13R itself may be a novel subunit of the IL-4R. Interleukin 13 (IL-13) shares many biological properties with IL-4, and although the receptor for IL-4 (IL-4R) has been characterized, the expression and structure of IL-13 receptor are unknown. We report here that human renal cell carcinoma (RCC) cells express large numbers of functional IL-13R. Human B lymphocytes and monocytes expressed a very small number of IL-13R, while resting or activated human T cells expressed little or no IL-13R. IL-4 did not compete for IL-13 binding, while IL-13 competed for IL-4 binding, even though IL-4R and IL-13R are structurally distinct on human RCC cells. IL-13 cross-linked with one major protein that is similar in size to the γcsubunit of IL-2, −4, −7, −9, and −15 receptors but was not recognized by anti-γcor anti-IL-4R antibodies. IL-4, on the other hand, cross-linked with two major proteins, the smaller of which appears to be similar in size to IL-13R and γc, but (like the IL-13R) it did not react with anti-γcantibody. Although as shown in this study and in previous studies, γcis a functional component of IL-4R in lymphoid cells, it does not appear to be associated with IL-4R on RCC cells. Even in the absence of common γ chain IL-4 and IL-13 were able to up-regulate intracellular adhesion molecule-1 antigen on RCC cells. These data suggest that the interaction of IL-13 with IL-4R does not involve γcand IL-13R itself may be a novel subunit of the IL-4R. IL-13 1The abbreviations used are:ILinterleukinIL-13R and IL-4Rinterleukin 13 and interleukin 4 receptor(s), respectivelyRCCrenal cell carcinomaICAM-1intercellular adhesion moleculeLAKlymphokine-activated killer. is a 12-kDa lymphokine that has been cloned from activated T cells (1Brown K.D. Zurawski S.M. Mosmann T.R. Zurawski G. J. Immunol. 1989; 142: 679-687PubMed Google Scholar, 2Minty A. Chalon P. Derocq J.-M. Dumont X. Guillemot J.-C. Kaghad M. Labit C. Leplatois P. Liauzun P. Miloux B. Minty C. Casellas P. Loison G. Lupker J. Shire D. Ferrara P. Caput D. Nature. 1993; 362: 248-250Crossref PubMed Scopus (869) Google Scholar). The gene for IL-13 is closely linked to the IL-4 gene (3Morgan J.G. Dolganov G.M. Robbins S.E. Hinton L.M. Lovett L.M. Nucleic Acids Res. 1992; 20: 5173-5179Crossref PubMed Scopus (182) Google Scholar), and IL-13 protein has been shown to have a 30% identity in the amino acid sequence to IL-4 protein (4Zurawski S.M. Vega Jr., F. Huyghe B. Zurawski G. EMBO J. 1993; 12: 2663-2670Crossref PubMed Scopus (451) Google Scholar). IL-13 shares many biological properties with IL-4. Like IL-4, it inhibits the production of inflammatory cytokines (2Minty A. Chalon P. Derocq J.-M. Dumont X. Guillemot J.-C. Kaghad M. Labit C. Leplatois P. Liauzun P. Miloux B. Minty C. Casellas P. Loison G. Lupker J. Shire D. Ferrara P. Caput D. Nature. 1993; 362: 248-250Crossref PubMed Scopus (869) Google Scholar, 5de Waal Malefyt R. Figdor C.G. Huijbens R. Mohan-Peterson S. Bennett B. Culpepper J. Dang W. Zurawski G. de Vries J.E. J. Immunol. 1993; 151: 6370-6381PubMed Google Scholar) and up-regulates major histocompatibility complex class II and CD23 expression on monocytes (6de Waal Malefyt R. Figdor C. de Vries J.E. Res. Immunol. 1993; 144: 629-633Crossref PubMed Scopus (43) Google Scholar). Similarly, on B cells, IL-13 enhances proliferative responses to anti-IgM and anti-CD40 antibodies, major histocompatibility complex class II, and CD23 expression, induces anti-CD40-dependent IgE class switch, and induces IgG and IgM synthesis (2Minty A. Chalon P. Derocq J.-M. Dumont X. Guillemot J.-C. Kaghad M. Labit C. Leplatois P. Liauzun P. Miloux B. Minty C. Casellas P. Loison G. Lupker J. Shire D. Ferrara P. Caput D. Nature. 1993; 362: 248-250Crossref PubMed Scopus (869) Google Scholar, 7McKenzie A.N.J. Culpepper J.A. de Waal Malefyt R. Briere F. Punnonen J. Aversa G. Sato A. Dang W. Cocks B.G. Menon S. de Vries J.E. Zurawski G. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3735-3739Crossref PubMed Scopus (543) Google Scholar, 8Defrance T. Carayon P. Billian G. Guillemot J.-C. Minty A. Caput D. Ferrara P. J. Exp. Med. 1994; 179: 135-143Crossref PubMed Scopus (266) Google Scholar, 9Punnonen J. Aversa G. Cocks B.G. Mckenzie A.N.J. Menon S. Zurawski G. de Waal Malefyt R. de Vries J.E. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3730-3734Crossref PubMed Scopus (991) Google Scholar, 10Cocks B.G. de Waal Malefyt R. Galizzi J.-P. de Vries J.E. Int. Immunol. 1993; 5: 657-663Crossref PubMed Scopus (245) Google Scholar). In sharp contrast to IL-4, IL-13 has been shown not to affect resting or activated T cells (9Punnonen J. Aversa G. Cocks B.G. Mckenzie A.N.J. Menon S. Zurawski G. de Waal Malefyt R. de Vries J.E. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3730-3734Crossref PubMed Scopus (991) Google Scholar, 11Zurawski G. de Vries J.E. Immunol. Today. 1994; 15: 19-26Abstract Full Text PDF PubMed Scopus (850) Google Scholar). interleukin interleukin 13 and interleukin 4 receptor(s), respectively renal cell carcinoma intercellular adhesion molecule lymphokine-activated killer. Despite the knowledge of many effects of IL-13, the receptor for IL-13 (IL-13R) has not been reported on. It was hypothesized that the γ subunit of the IL-2 receptor (IL-2Rγc) (12Takeshita T. Asao H. Ohtani K. Ishii N. Kumaki S. Tanaka N. Munakata H. Nakamura M. Sugamura K. Science. 1992; 257: 379-382Crossref PubMed Scopus (853) Google Scholar, 13Voss S.D. Sondel P.M. Robb R.J. J. Exp. Med. 1992; 176: 531-541Crossref PubMed Scopus (140) Google Scholar), which is associated with IL-4, IL-7, IL-9, and IL-15 (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar, 15Kondo M. Takeshita T. Ishii N. Nakamura M. Watanabe S. Arai K. Sugamura K. Science. 1993; 262: 1874-1877Crossref PubMed Scopus (751) Google Scholar, 16Noguchi M. Adelstein S. Cao X. Leonard W. Science. 1993; 262: 1877-1880Crossref PubMed Scopus (806) Google Scholar, 17Kondo M. Takeshita T. Higuchi M. Nakamura M. Sudo T. Nishikawa S. Sugamura K. Science. 1994; 263: 1453-1454Crossref PubMed Scopus (358) Google Scholar, 18Giri J.G. Ahdieh M. Eisenman J. Shanebeck K. Grabstein K. Kumaki S. Namen A. Park L.S. Cosman D. Anderson D. EMBO J. 1994; 13: 2822-2830Crossref PubMed Scopus (979) Google Scholar) receptors, may also be associated with IL-13R (12Takeshita T. Asao H. Ohtani K. Ishii N. Kumaki S. Tanaka N. Munakata H. Nakamura M. Sugamura K. Science. 1992; 257: 379-382Crossref PubMed Scopus (853) Google Scholar, 13Voss S.D. Sondel P.M. Robb R.J. J. Exp. Med. 1992; 176: 531-541Crossref PubMed Scopus (140) Google Scholar, 14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar, 15Kondo M. Takeshita T. Ishii N. Nakamura M. Watanabe S. Arai K. Sugamura K. Science. 1993; 262: 1874-1877Crossref PubMed Scopus (751) Google Scholar, 31Russell S.M. Johnson J.A. Noguchi M.K. Bacon C.M. Friedman M. Berg M. McVicar D.W. Witthuhn B.A. Silvennoinen O. Goldman A.S. Schmalstieg F.C. Ihle J.N. O'Shea J.J. Leonard W.J. Science. 1994; 266: 1042-1045Crossref PubMed Scopus (614) Google Scholar). In addition, others have suggested that IL-4R and IL-13R may share a common component that appears to function in signal transduction (4Zurawski S.M. Vega Jr., F. Huyghe B. Zurawski G. EMBO J. 1993; 12: 2663-2670Crossref PubMed Scopus (451) Google Scholar). We have previously demonstrated that human renal cell carcinoma (RCC) cells express high affinity IL-4R (19Obiri N.I. Hillman G.G. Haas G.P. Sud S. Puri R.K. J. Clin. Invest. 1993; 91: 88-93Crossref PubMed Scopus (177) Google Scholar). Since many of the observed effects of IL-13 are similar to those of IL-4, we have examined RCC cells for the expression of IL-13R. We demonstrate that human RCC cells express large numbers of functional IL-13R and that IL-4 and IL-13 interact with each other's receptors. We provide evidence that IL-13R and IL-4R on RCC cells are composed of different subunits and that IL-13R is mainly composed of a single protein similar in size to the smaller of the two IL-4R subunits. The IL-13R protein does not cross-react with anti-γcor anti-IL-4R antibodies. Similarly, to our surprise, the smaller of the two IL-4R proteins does not react with anti-γcantibody. These results suggest that γcchain is not associated with IL-13R or IL-4R on human RCC cells and further suggest that IL-13R is a monomeric or dimeric protein, which itself may be a novel subunit of IL-4R. Recombinant human IL-13 (2Minty A. Chalon P. Derocq J.-M. Dumont X. Guillemot J.-C. Kaghad M. Labit C. Leplatois P. Liauzun P. Miloux B. Minty C. Casellas P. Loison G. Lupker J. Shire D. Ferrara P. Caput D. Nature. 1993; 362: 248-250Crossref PubMed Scopus (869) Google Scholar) was kindly provided by Dr. A. Minty (Sanofi Elf Bio Recherches, Laberge, France). For some experiments, we used recombinant human IL-13 expressed in Escherichia coli and produced by one of us (W. D.). Prior to use, we compared IL-13 prepared from the two sources and found that they were identical in biological activity (i.e. support of TF-1 cell proliferation) as well as in their ability to displace 125I-IL-13 from the cell surface. Recombinant human IL-4 was provided by Paul Trotta (Schering-Plough Research Institute, Kenilworth, NJ). A polyclonal rabbit antibody to the high affinity human IL-4R (P7) was a kind gift from Immunex Corporation (Seattle, WA). The antibodies to human IL-4 and intercellular adhesion molecule (ICAM-1) were purchased from Genzyme Corp. (Boston, MA) and AMAC, Inc. (Westbrook, ME), respectively. The ICAM-1 cDNA probe, a 1.9-kilobase cDNA cloned from stimulated HL-60 cells (20Simmons D. Makgoba M.W. Seed B. Nature. 1988; 331: 624-627Crossref PubMed Scopus (563) Google Scholar), was a gift from Dr. Steve Shaw (NCI, Bethesda, MD). The primary cultures of renal cell carcinoma cell lines WS-RCC, HL-RCC, and MA-RCC were established in our laboratory and are maintained as described previously (19Obiri N.I. Hillman G.G. Haas G.P. Sud S. Puri R.K. J. Clin. Invest. 1993; 91: 88-93Crossref PubMed Scopus (177) Google Scholar). TF-1 cell line, a human premyeloid erythroleukemic cell line that responds to various cytokines including IL-13 (4Zurawski S.M. Vega Jr., F. Huyghe B. Zurawski G. EMBO J. 1993; 12: 2663-2670Crossref PubMed Scopus (451) Google Scholar), and other cells were cultured in RPMI 1640 medium containing 10% fetal bovine serum glutamine (2 m M), sodium pyruvate (1 m M), essential amino acids (1 m M), penicillin (100 units/ml), and streptomycin (100 μg/ml). Recombinant human IL-4 and recombinant human IL-13 were labeled with 125I (Amersham Corp.) by using the IODO-GEN reagent (Pierce) according to the manufacturer's instructions. The specific activity of the cytokines was to from to of For experiments, cells were for with 125I-IL-13 (100 with or to of In some experiments, IL-13R expression was examined as described previously (19Obiri N.I. Hillman G.G. Haas G.P. Sud S. Puri R.K. J. Clin. Invest. 1993; 91: 88-93Crossref PubMed Scopus (177) Google Scholar). The data were with the D. PubMed Scopus Google Scholar) to receptor number and were labeled with 125I-IL-13 or in the or absence of IL-13 or IL-4 for The was cross-linked to receptor with (Pierce) a of m for were in a containing m m m m m and The cell were by in containing and by The was and In some experiments, the complex was from the by with protein that been with IL-4R or and as RCC cells were cultured with IL-13 a and for with ICAM-1 antibody cells were in or with were and for with a antibody of of IgG to cells were on using a II was expressed as number on a of were examined by (19Obiri N.I. Hillman G.G. Haas G.P. Sud S. Puri R.K. J. Clin. Invest. 1993; 91: 88-93Crossref PubMed Scopus (177) Google Scholar, J. T. A Scholar). The was with cDNA for ICAM-1 for In some experiments, the was and with a cDNA for human RCC lines HL-RCC, and that were examined 125I-IL-13 and the of IL-13R from in cells to in cells and G. N. Y. Acad. Sci. Scopus Google Scholar) that one affinity class of receptors was expressed on each cell The and in RCC cell while cells expressed affinity receptors of IL-13R on human of IL-13R on human cells Although IL-13 has previously been reported in human B cells, and premyeloid cells (2Minty A. Chalon P. Derocq J.-M. Dumont X. Guillemot J.-C. Kaghad M. Labit C. Leplatois P. Liauzun P. Miloux B. Minty C. Casellas P. Loison G. Lupker J. Shire D. Ferrara P. Caput D. Nature. 1993; 362: 248-250Crossref PubMed Scopus (869) Google Scholar, J.G. Dolganov G.M. Robbins S.E. Hinton L.M. Lovett L.M. Nucleic Acids Res. 1992; 20: 5173-5179Crossref PubMed Scopus (182) Google Scholar, S.M. Vega Jr., F. Huyghe B. Zurawski G. EMBO J. 1993; 12: 2663-2670Crossref PubMed Scopus (451) Google Scholar, 5de Waal Malefyt R. Figdor C.G. Huijbens R. Mohan-Peterson S. Bennett B. Culpepper J. Dang W. Zurawski G. de Vries J.E. J. Immunol. 1993; 151: 6370-6381PubMed Google Scholar, Waal Malefyt R. Figdor C. de Vries J.E. Res. Immunol. 1993; 144: 629-633Crossref PubMed Scopus (43) Google Scholar, 7McKenzie A.N.J. Culpepper J.A. de Waal Malefyt R. Briere F. Punnonen J. Aversa G. Sato A. Dang W. Cocks B.G. Menon S. de Vries J.E. Zurawski G. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3735-3739Crossref PubMed Scopus (543) Google Scholar, 8Defrance T. Carayon P. Billian G. Guillemot J.-C. Minty A. Caput D. Ferrara P. J. Exp. Med. 1994; 179: 135-143Crossref PubMed Scopus (266) Google Scholar, 9Punnonen J. Aversa G. Cocks B.G. Mckenzie A.N.J. Menon S. Zurawski G. de Waal Malefyt R. de Vries J.E. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3730-3734Crossref PubMed Scopus (991) Google Scholar, 10Cocks B.G. de Waal Malefyt R. Galizzi J.-P. de Vries J.E. Int. Immunol. 1993; 5: 657-663Crossref PubMed Scopus (245) Google Scholar, 11Zurawski G. de Vries J.E. Immunol. Today. 1994; 15: 19-26Abstract Full Text PDF PubMed Scopus (850) Google Scholar), little is IL-13R structure or in cells. results that human B cell line, and TF-1 cell line express very IL-13 compared with human RCC cells the other hand, no of 125I-IL-13 was observed on T cells, cells, and resting or is with the that IL-13 has not been observed in T lymphocytes (9Punnonen J. Aversa G. Cocks B.G. Mckenzie A.N.J. Menon S. Zurawski G. de Waal Malefyt R. de Vries J.E. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3730-3734Crossref PubMed Scopus (991) Google Scholar, 11Zurawski G. de Vries J.E. Immunol. Today. 1994; 15: 19-26Abstract Full Text PDF PubMed Scopus (850) Google Scholar). it was that γcis associated with IL-13R (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar, 15Kondo M. Takeshita T. Ishii N. Nakamura M. Watanabe S. Arai K. Sugamura K. Science. 1993; 262: 1874-1877Crossref PubMed Scopus (751) Google Scholar, 17Kondo M. Takeshita T. Higuchi M. Nakamura M. Sudo T. Nishikawa S. Sugamura K. Science. 1994; 263: 1453-1454Crossref PubMed Scopus (358) Google Scholar, 18Giri J.G. Ahdieh M. Eisenman J. Shanebeck K. Grabstein K. Kumaki S. Namen A. Park L.S. Cosman D. Anderson D. EMBO J. 1994; 13: 2822-2830Crossref PubMed Scopus (979) Google Scholar) and that IL-13R may share a common component with IL-4R (4Zurawski S.M. Vega Jr., F. Huyghe B. Zurawski G. EMBO J. 1993; 12: 2663-2670Crossref PubMed Scopus (451) Google Scholar, G. Punnonen J. Cocks B.G. de Waal Malefyt R. Vega Jr., F. Zurawski S.M. Zurawski G. de Vries J.E. J. Exp. Med. 1993; PubMed Scopus Google Scholar). we on and cells using or 125I-IL-13 in the or absence of of results that IL-4 from to RCC cells and of in and HL-RCC, IL-13, which also to cells of in and in similar the other hand, while 125I-IL-13 was by IL-13 of the in cell it was by IL-4 of in and in These results that IL-4 and IL-13 interact with each other's the interaction is not IL-4 of 125I-IL-13 was and IL-13 of was not results with previous in which IL-13 was found to compete with IL-4 on TF-1 cells (4Zurawski S.M. Vega Jr., F. Huyghe B. Zurawski G. EMBO J. 1993; 12: 2663-2670Crossref PubMed Scopus (451) Google Scholar). in that report the was not we provide results that even though IL-13 competed for IL-4 binding, IL-4 did not compete for IL-13 We also IL-13 for the IL-4 on lymphoid cells or cell These cells were with IL-4 with or IL-4 or shown in A and to and cells, and IL-4 IL-4, while IL-13 not compete this is to that with RCC cells in which IL-13 competed for IL-4 The of IL-13 to compete for to is with our that IL-13 did not to T cells. the of IL-13 to compete for IL-4 on the cell cell line is not cells express common γ and it is that common γ chain with the of are to this We the subunit structure of IL-13R on RCC cells by results that 125I-IL-13 cross-linked to one major protein on RCC cells and that the complex as a single and A and A single was also observed on human premyeloid cells 4 of the the of IL-13 the size of the IL-13 protein was The 125I-IL-13 cross-linked was not observed the was in the of a of IL-13 for each cell line, and In to the major a of was also observed in and but not on MA-RCC cells 4 to be associated with IL-13R, IL-13 competed for the of protein or a of the In contrast to the of 125I-IL-13 by IL-13 of IL-4 did not the of IL-13R in RCC cell lines 4 for each IL-13 on the other competed for to major proteins on cells 4 It is of that 125I-IL-13 cross-linked protein was in size in WS-RCC, and cell lines compared with that in MA-RCC A and and A and as or may for this of IL-13R and IL-4R. RCC or cells were labeled with 125I-IL-13 or in the absence or of IL-13 or IL-4. The cell were with the anti-IL-4R (P7) or to IL-4R or γcand on IL-13 to MA-RCC cells in the absence or of IL-13 or with anti-IL-4R or 125I-IL-13 cross-linked to cells in the absence or of IL-13 or with IL-4R or cross-linked to cells in the absence or of IL-4 or with antibody to IL-4R and or to 4 of receptors on cells by anti-γcantibody. of was from RCC and two T cell one cell line, or a cell line and was These were with a M. Adelstein S. Cao X. Leonard W.J. J. 1993; Full Text PDF PubMed Google Scholar) and to for the IL-4R and IL-13R, we and with the polyclonal anti-IL-4R which has been used to IL-4R subunits (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar). results that anti-IL-4R did not IL-13R on MA-RCC cells or cells IL-13R is not with the anti-IL-4R as anti-IL-4R antibody IL-4R and on cells which express IL-4R (19Obiri N.I. Hillman G.G. Haas G.P. Sud S. Puri R.K. J. Clin. Invest. 1993; 91: 88-93Crossref PubMed Scopus (177) Google Scholar). We IL-13R and IL-4R on RCC cells with anti-γcantibody. to the been shown to IL-4R and (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar, 16Noguchi M. Adelstein S. Cao X. Leonard W. Science. 1993; 262: 1877-1880Crossref PubMed Scopus (806) Google Scholar). this antibody did not the IL-13R on MA-RCC cells or on a the IL-4R on lymphoid cells (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar) Although been shown to be associated with IL-4R on lymphoid cells (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar, 15Kondo M. Takeshita T. Ishii N. Nakamura M. Watanabe S. Arai K. Sugamura K. Science. 1993; 262: 1874-1877Crossref PubMed Scopus (751) Google Scholar), it does not appear to be associated with the IL-4R on cells not IL-4R on cells The absence of on RCC cells was by RCC cell lines examined were for while lymphoid cells were The of of γcchain with IL-4R in RCC cells is a novel and in the absence of were functional on cells as IL-4 their in (19Obiri N.I. Hillman G.G. Haas G.P. Sud S. Puri R.K. J. Clin. Invest. 1993; 91: 88-93Crossref PubMed Scopus (177) Google Scholar) and ICAM-1 antigen expression N. and R. K. Puri Int. J. Similarly, we previously demonstrated that cells, which express not express common γcchain (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar). the of γ chain cells the of which was not observed in cells, that γcchain is for These data suggest that IL-4 may involve two The of two has also been previously suggested S.M. Int. Immunol. PubMed Scopus Google Scholar, M. C. M. A. K. J. Immunol. 1989; PubMed Scopus Google Scholar). In addition, in a study cell lines and that have many properties in common with human it was demonstrated that IL-4 even though cells did not express common γcchain by chain (12Takeshita T. Asao H. Ohtani K. Ishii N. Kumaki S. Tanaka N. Munakata H. Nakamura M. Sugamura K. Science. 1992; 257: 379-382Crossref PubMed Scopus (853) Google Scholar, H. D.W. 1994; PubMed Google Scholar). These data that IL-4R is of different receptor in different cell and that they are able to signal by different data that IL-13R not with γcchain of IL-2, IL-4, IL-7, IL-9, and in RCC cells. Since RCC cells did not express this it is that γcchain with IL-13R in other cells. The of IL-13R with γcchain was in cells that expressed this Human B cells and T cells, including cells, have been shown to express γcchain (14Russell S.M. Keegan A.D. Harada N. Nakamura Y. Noguchi M. Leland P. Freedman M.C. Miyajima A. Puri R.K. Paul W.E. Leonard W.J. Science. 1993; 262: 1880-1883Crossref PubMed Scopus (760) Google Scholar, 15Kondo M. Takeshita T. Ishii N. Nakamura M. Watanabe S. Arai K. Sugamura K. Science. 1993; 262: 1874-1877Crossref PubMed Scopus (751) Google Scholar). Since cells expressed no or IL-13 and very to the it is to receptor structure by the that IL-13 did not compete for IL-4 on cells that common γcchain does not with IL-13R. In addition, the of to cells γcchain also that γcchain does not interact with IL-13R. We have previously shown that RCC cells express high of ICAM-1 antigen on their cell which is by shown in A and and expressed of and with IL-13 this The IL-13 of ICAM-1 expression was also the as shown in C. data were to we observed that IL-13 a in ICAM-1 compared with by IL-4 and by a These data demonstrate that IL-13 on RCC cells is We have demonstrated that human RCC cells express and numbers of functional high or affinity IL-13R cells. Although IL-13 appears to interact with IL-4 has interaction with IL-13R. The subunit structure of IL-13R appears to be different from that of IL-4R. 125I-IL-13 to a major protein of while to two different proteins of and Even though the of IL-13R and one of the two proteins of the IL-4R are similar to those of the γcsubunit of and did not cross-react with IL-13R or with IL-4R on RCC cells. The absence of by the of for RCC cells. These data suggest that the of IL-4R on RCC cells is different from that on cells that express of the in the size of IL-13R and one subunit of it is that IL-13R is a component of the which may be one for IL-13 interact with IL-4R in RCC cells as shown in this study and in TF-1 cells as shown by Zurawski (4Zurawski S.M. Vega Jr., F. Huyghe B. Zurawski G. EMBO J. 1993; 12: 2663-2670Crossref PubMed Scopus (451) Google Scholar). are to support or this