Abstract
We investigated the biological role of the human tumor necrosis factor p75 (hTNF-R75), making use of the species specificity of TNF responses in murine (m) T cell lines. Several TNF-mediated activities on mouse T cells, such as cytokine induction or proliferation, showed a 100-500- fold difference in specific biological activity between mTNF and hTNF. After transfection of hTNF-R75 cDNA in a rat/mouse T cell hybridoma (PC60), however, the 100-fold lower specific biological activity of hTNF was converted to the same specific biological activity as mTNF. The TNF-mediated induction of granulocyte/macrophage colony-stimulating factor was strongly synergized by the addition of interleukin 1. In the presence of the latter cytokine, ligand-competing monoclonal antibodies against hTNF-R75 (utr-1, utr-2, utr-3) were agonistic on transfected PC60 cells. This agonistic activity was further enhanced by crosslinking with sheep anti-murine immunoglobulin antibodies. These data provide direct evidence for a functional role of TNF-R75, without ligand-dependent TNF-R55 involvement, in the induction of cytokine secretion in T cells.
Full Text
The Full Text of this article is available as a PDF (877.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arakawa T., Yphantis D. A. Molecular weight of recombinant human tumor necrosis factor-alpha. J Biol Chem. 1987 Jun 5;262(16):7484–7485. [PubMed] [Google Scholar]
- Barrett K., Taylor-Fishwick D. A., Cope A. P., Kissonerghis A. M., Gray P. W., Feldmann M., Foxwell B. M. Cloning, expression and cross-linking analysis of the murine p55 tumor necrosis factor receptor. Eur J Immunol. 1991 Jul;21(7):1649–1656. doi: 10.1002/eji.1830210710. [DOI] [PubMed] [Google Scholar]
- Beutler B., Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. doi: 10.1146/annurev.iy.07.040189.003205. [DOI] [PubMed] [Google Scholar]
- Brockhaus M., Schoenfeld H. J., Schlaeger E. J., Hunziker W., Lesslauer W., Loetscher H. Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3127–3131. doi: 10.1073/pnas.87.8.3127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conlon P. J. A rapid biologic assay for the detection of interleukin 1. J Immunol. 1983 Sep;131(3):1280–1282. [PubMed] [Google Scholar]
- Conzelmann A., Corthésy P., Cianfriglia M., Silva A., Nabholz M. Hybrids between rat lymphoma and mouse T cells with inducible cytolytic activity. Nature. 1982 Jul 8;298(5870):170–172. doi: 10.1038/298170a0. [DOI] [PubMed] [Google Scholar]
- DeLamarter J. F., Mermod J. J., Liang C. M., Eliason J. F., Thatcher D. R. Recombinant murine GM-CSF from E. coli has biological activity and is neutralized by a specific antiserum. EMBO J. 1985 Oct;4(10):2575–2581. doi: 10.1002/j.1460-2075.1985.tb03973.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dembic Z., Loetscher H., Gubler U., Pan Y. C., Lahm H. W., Gentz R., Brockhaus M., Lesslauer W. Two human TNF receptors have similar extracellular, but distinct intracellular, domain sequences. Cytokine. 1990 Jul;2(4):231–237. doi: 10.1016/1043-4666(90)90022-l. [DOI] [PubMed] [Google Scholar]
- Ehrke M. J., Ho R. L., Hori K. Species-specific TNF induction of thymocyte proliferation. Cancer Immunol Immunother. 1988;27(2):103–108. doi: 10.1007/BF00200012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engelmann H., Holtmann H., Brakebusch C., Avni Y. S., Sarov I., Nophar Y., Hadas E., Leitner O., Wallach D. Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity. J Biol Chem. 1990 Aug 25;265(24):14497–14504. [PubMed] [Google Scholar]
- Erard F., Corthesy P., Smith K. A., Fiers W., Conzelmann A., Nabholz M. Characterization of soluble factors that induce the cytolytic activity and the expression of T cell growth factor receptors of a T cell hybrid. J Exp Med. 1984 Aug 1;160(2):584–599. doi: 10.1084/jem.160.2.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erikstein B. K., Smeland E. B., Blomhoff H. K., Funderud S., Prydz K., Lesslauer W., Espevik T. Independent regulation of 55-kDa and 75-kDa tumor necrosis factor receptors during activation of human peripheral blood B lymphocytes. Eur J Immunol. 1991 Apr;21(4):1033–1037. doi: 10.1002/eji.1830210426. [DOI] [PubMed] [Google Scholar]
- Espevik T., Brockhaus M., Loetscher H., Nonstad U., Shalaby R. Characterization of binding and biological effects of monoclonal antibodies against a human tumor necrosis factor receptor. J Exp Med. 1990 Feb 1;171(2):415–426. doi: 10.1084/jem.171.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Everaerdt B., Brouckaert P., Shaw A., Fiers W. Four different interleukin-1 species sensitize to the lethal action of tumour necrosis factor. Biochem Biophys Res Commun. 1989 Aug 30;163(1):378–385. doi: 10.1016/0006-291x(89)92146-3. [DOI] [PubMed] [Google Scholar]
- Fiers W., Brouckaert P., Devos R., Fransen L., Leroux-Roels G., Remaut E., Suffys P., Tavernier J., Van der Heyden J., Van Roy F. Lymphokines and monokines in anti-cancer therapy. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):587–595. doi: 10.1101/sqb.1986.051.01.071. [DOI] [PubMed] [Google Scholar]
- Fiers W. Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Lett. 1991 Jul 22;285(2):199–212. doi: 10.1016/0014-5793(91)80803-b. [DOI] [PubMed] [Google Scholar]
- Goodwin R. G., Anderson D., Jerzy R., Davis T., Brannan C. I., Copeland N. G., Jenkins N. A., Smith C. A. Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor. Mol Cell Biol. 1991 Jun;11(6):3020–3026. doi: 10.1128/mcb.11.6.3020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hohmann H. P., Brockhaus M., Baeuerle P. A., Remy R., Kolbeck R., van Loon A. P. Expression of the types A and B tumor necrosis factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-kappa B. TNF alpha is not needed for induction of a biological effect via TNF receptors. J Biol Chem. 1990 Dec 25;265(36):22409–22417. [PubMed] [Google Scholar]
- Hohmann H. P., Remy R., Brockhaus M., van Loon A. P. Two different cell types have different major receptors for human tumor necrosis factor (TNF alpha). J Biol Chem. 1989 Sep 5;264(25):14927–14934. [PubMed] [Google Scholar]
- Hopkins S. J., Humphreys M. Simple, sensitive and specific bioassay of interleukin-1. J Immunol Methods. 1989 Jun 21;120(2):271–276. doi: 10.1016/0022-1759(89)90252-4. [DOI] [PubMed] [Google Scholar]
- Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
- Kramer S. M., Aggarwal B. B., Eessalu T. E., McCabe S. M., Ferraiolo B. L., Figari I. S., Palladino M. A., Jr Characterization of the in vitro and in vivo species preference of human and murine tumor necrosis factor-alpha. Cancer Res. 1988 Feb 15;48(4):920–925. [PubMed] [Google Scholar]
- Lewis M., Tartaglia L. A., Lee A., Bennett G. L., Rice G. C., Wong G. H., Chen E. Y., Goeddel D. V. Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2830–2834. doi: 10.1073/pnas.88.7.2830. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewit-Bentley A., Fourme R., Kahn R., Prangé T., Vachette P., Tavernier J., Hauquier G., Niers W. Structure of tumour necrosis factor by X-ray solution scattering and preliminary studies by single crystal X-ray diffraction. J Mol Biol. 1988 Jan 20;199(2):389–392. doi: 10.1016/0022-2836(88)90323-3. [DOI] [PubMed] [Google Scholar]
- Loetscher H., Pan Y. C., Lahm H. W., Gentz R., Brockhaus M., Tabuchi H., Lesslauer W. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell. 1990 Apr 20;61(2):351–359. doi: 10.1016/0092-8674(90)90815-v. [DOI] [PubMed] [Google Scholar]
- Loetscher H., Steinmetz M., Lesslauer W. Tumor necrosis factor: receptors and inhibitors. Cancer Cells. 1991 Jun;3(6):221–226. [PubMed] [Google Scholar]
- Naume B., Shalaby R., Lesslauer W., Espevik T. Involvement of the 55- and 75-kDa tumor necrosis factor receptors in the generation of lymphokine-activated killer cell activity and proliferation of natural killer cells. J Immunol. 1991 May 1;146(9):3045–3048. [PubMed] [Google Scholar]
- Oppenheim J. J., Matsushima K., Yoshimura T., Leonard E. J., Neta R. Relationship between interleukin 1 (IL1), tumor necrosis factor (TNF) and a neutrophil attracting peptide (NAP-1). Agents Actions. 1989 Jan;26(1-2):134–140. doi: 10.1007/BF02126586. [DOI] [PubMed] [Google Scholar]
- Plaetinck G., Declercq W., Tavernier J., Nabholz M., Fiers W. Recombinant tumor necrosis factor can induce interleukin 2 receptor expression and cytolytic activity in a rat x mouse T cell hybrid. Eur J Immunol. 1987 Dec;17(12):1835–1838. doi: 10.1002/eji.1830171224. [DOI] [PubMed] [Google Scholar]
- Ranges G. E., Bombara M. P., Aiyer R. A., Rice G. G., Palladino M. A., Jr Tumor necrosis factor-alpha as a proliferative signal for an IL-2-dependent T cell line: strict species specificity of action. J Immunol. 1989 Feb 15;142(4):1203–1208. [PubMed] [Google Scholar]
- Ranges G. E., Zlotnik A., Espevik T., Dinarello C. A., Cerami A., Palladino M. A., Jr Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines. J Exp Med. 1988 Apr 1;167(4):1472–1478. doi: 10.1084/jem.167.4.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schall T. J., Lewis M., Koller K. J., Lee A., Rice G. C., Wong G. H., Gatanaga T., Granger G. A., Lentz R., Raab H. Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell. 1990 Apr 20;61(2):361–370. doi: 10.1016/0092-8674(90)90816-w. [DOI] [PubMed] [Google Scholar]
- Shalaby M. R., Sundan A., Loetscher H., Brockhaus M., Lesslauer W., Espevik T. Binding and regulation of cellular functions by monoclonal antibodies against human tumor necrosis factor receptors. J Exp Med. 1990 Nov 1;172(5):1517–1520. doi: 10.1084/jem.172.5.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith C. A., Davis T., Anderson D., Solam L., Beckmann M. P., Jerzy R., Dower S. K., Cosman D., Goodwin R. G. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019–1023. doi: 10.1126/science.2160731. [DOI] [PubMed] [Google Scholar]
- Tada H., Shiho O., Kuroshima K., Koyama M., Tsukamoto K. An improved colorimetric assay for interleukin 2. J Immunol Methods. 1986 Nov 6;93(2):157–165. doi: 10.1016/0022-1759(86)90183-3. [DOI] [PubMed] [Google Scholar]
- Tartaglia L. A., Goeddel D. V. Two TNF receptors. Immunol Today. 1992 May;13(5):151–153. doi: 10.1016/0167-5699(92)90116-O. [DOI] [PubMed] [Google Scholar]
- Tartaglia L. A., Weber R. F., Figari I. S., Reynolds C., Palladino M. A., Jr, Goeddel D. V. The two different receptors for tumor necrosis factor mediate distinct cellular responses. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9292–9296. doi: 10.1073/pnas.88.20.9292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thoma B., Grell M., Pfizenmaier K., Scheurich P. Identification of a 60-kD tumor necrosis factor (TNF) receptor as the major signal transducing component in TNF responses. J Exp Med. 1990 Oct 1;172(4):1019–1023. doi: 10.1084/jem.172.4.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
- Van Ostade X., Tavernier J., Prangé T., Fiers W. Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis. EMBO J. 1991 Apr;10(4):827–836. doi: 10.1002/j.1460-2075.1991.tb08015.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vandenabeele P., Declercq W., Libert C., Fiers W. Development of a simple, sensitive and specific bioassay for interleukin-1 based on the proliferation of RPMI 1788 cells. Comparison with other bioassays for IL-1. J Immunol Methods. 1990 Dec 31;135(1-2):25–32. doi: 10.1016/0022-1759(90)90252-q. [DOI] [PubMed] [Google Scholar]
- Vandenabeele P., Guisez Y., Declercq W., Bauw G., Vandekerckhove J., Fiers W. Response of murine cell lines to an IL-1/IL-2-induced factor in a rat/mouse T hybridoma (PC60): differential induction of cytokines by human IL-1 alpha and IL-1 beta and partial amino acid sequence of rat GM-CSF. Lymphokine Res. 1990 Fall;9(3):381–389. [PubMed] [Google Scholar]
- Waage A., Espevik T. Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice. J Exp Med. 1988 Jun 1;167(6):1987–1992. doi: 10.1084/jem.167.6.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waage A., Halstensen A., Shalaby R., Brandtzaeg P., Kierulf P., Espevik T. Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. J Exp Med. 1989 Dec 1;170(6):1859–1867. doi: 10.1084/jem.170.6.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willard-Gallo K. E., Van de Keere F., Kettmann R. A specific defect in CD3 gamma-chain gene transcription results in loss of T-cell receptor/CD3 expression late after human immunodeficiency virus infection of a CD4+ T-cell line. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6713–6717. doi: 10.1073/pnas.87.17.6713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wingfield P., Pain R. H., Craig S. Tumour necrosis factor is a compact trimer. FEBS Lett. 1987 Jan 26;211(2):179–184. doi: 10.1016/0014-5793(87)81432-1. [DOI] [PubMed] [Google Scholar]
- de la Luna S., Soria I., Pulido D., Ortín J., Jiménez A. Efficient transformation of mammalian cells with constructs containing a puromycin-resistance marker. Gene. 1988;62(1):121–126. doi: 10.1016/0378-1119(88)90585-9. [DOI] [PubMed] [Google Scholar]