Abstract
Interleukin-HP1 (HP1)/IL-6 is a 25-30-kD protein produced by macrophages, fibroblasts, and certain T cell lines. It was originally identified as a mouse growth factor for B cell hybridomas and plasmacytomas, and was recently shown to stimulate growth and differentiation of normal B cells. Here we demonstrate that, in the presence of lectins or anti-T cell receptor antibodies, HP1/IL-6 has a growth factor activity equivalent to that of IL-2 for mature thymic and peripheral T cells of both the L3T4+ and Lyt-2+ subsets. Contrary to IL- 2 and IL-4, HP1/IL-6 was, however, not capable of supporting the growth of established T cell lines. In addition to its effects on T cell proliferation, HP1/IL-6 also enhanced the differentiation of mouse cytolytic T cell precursors in primary allogeneic mixed lymphocyte cultures. Fractionation of responding cell populations indicated that HP1/IL-6 was capable of restoring the response of accessory cell- depleted T cells to Con A. This observation suggests that the production of HP1/IL-6 by macrophages could, at least partly, explain their role in polyclonal T cell activation.
Full Text
The Full Text of this article is available as a PDF (698.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bazin H., Xhurdebise L. M., Burtonboy G., Lebacq A. M., De Clercq L., Cormont F. Rat monoclonal antibodies. I. Rapid purification from in vitro culture supernatants. J Immunol Methods. 1984 Feb 10;66(2):261–269. doi: 10.1016/0022-1759(84)90337-5. [DOI] [PubMed] [Google Scholar]
- Brakenhoff J. P., de Groot E. R., Evers R. F., Pannekoek H., Aarden L. A. Molecular cloning and expression of hybridoma growth factor in Escherichia coli. J Immunol. 1987 Dec 15;139(12):4116–4121. [PubMed] [Google Scholar]
- Cayphas S., Van Damme J., Vink A., Simpson R. J., Billiau A., Van Snick J. Identification of an interleukin HP1-like plasmacytoma growth factor produced by L cells in response to viral infection. J Immunol. 1987 Nov 1;139(9):2965–2969. [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]
- Coulie P. G., Cayphas S., Vink A., Uyttenhove C., Van Snick J. Interleukin-HP1-related hybridoma and plasmacytoma growth factors induced by lipopolysaccharide in vivo. Eur J Immunol. 1987 Aug;17(8):1217–1220. doi: 10.1002/eji.1830170821. [DOI] [PubMed] [Google Scholar]
- Devos R., Plaetinck G., Cheroutre H., Simons G., Degrave W., Tavernier J., Remaut E., Fiers W. Molecular cloning of human interleukin 2 cDNA and its expression in E. coli. Nucleic Acids Res. 1983 Jul 11;11(13):4307–4323. doi: 10.1093/nar/11.13.4307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
- Garman R. D., Jacobs K. A., Clark S. C., Raulet D. H. B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7629–7633. doi: 10.1073/pnas.84.21.7629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garman R. D., Raulet D. H. Characterization of a novel murine T cell-activating factor. J Immunol. 1987 Feb 15;138(4):1121–1129. [PubMed] [Google Scholar]
- Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Habu S., Raff M. C. Accessory cell dependence of lectin-induced proliferation of mouse T lymphocytes. Eur J Immunol. 1977 Jul;7(7):451–457. doi: 10.1002/eji.1830070710. [DOI] [PubMed] [Google Scholar]
- Haegeman G., Content J., Volckaert G., Derynck R., Tavernier J., Fiers W. Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Eur J Biochem. 1986 Sep 15;159(3):625–632. doi: 10.1111/j.1432-1033.1986.tb09931.x. [DOI] [PubMed] [Google Scholar]
- Hardt C., Sato N., Wagner H. Functional and biochemical characteristics of a murine interleukin 2 receptor-inducing factor. Eur J Immunol. 1987 Feb;17(2):209–216. doi: 10.1002/eji.1830170210. [DOI] [PubMed] [Google Scholar]
- Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
- Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Männel D. N., Mizel S. B., Diamantstein T., Falk W. Induction of interleukin 2 responsiveness in thymocytes by synergistic action of interleukin 1 and interleukin 2. J Immunol. 1985 May;134(5):3108–3110. [PubMed] [Google Scholar]
- Nordan R. P., Potter M. A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science. 1986 Aug 1;233(4763):566–569. doi: 10.1126/science.3726549. [DOI] [PubMed] [Google Scholar]
- Nordan R. P., Pumphrey J. G., Rudikoff S. Purification and NH2-terminal sequence of a plasmacytoma growth factor derived from the murine macrophage cell line P388D1. J Immunol. 1987 Aug 1;139(3):813–817. [PubMed] [Google Scholar]
- Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
- Poupart P., Vandenabeele P., Cayphas S., Van Snick J., Haegeman G., Kruys V., Fiers W., Content J. B cell growth modulating and differentiating activity of recombinant human 26-kd protein (BSF-2, HuIFN-beta 2, HPGF). EMBO J. 1987 May;6(5):1219–1224. doi: 10.1002/j.1460-2075.1987.tb02357.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raulet D. H., Hünig T., Parker D. C. T cells produce TRF in response to Con A and factors in T cell hybridoma supernatants. J Immunol. 1982 Feb;128(2):908–912. [PubMed] [Google Scholar]
- Taga T., Kawanishi Y., Hardy R. R., Hirano T., Kishimoto T. Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression. J Exp Med. 1987 Oct 1;166(4):967–981. doi: 10.1084/jem.166.4.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Damme J., Opdenakker G., Simpson R. J., Rubira M. R., Cayphas S., Vink A., Billiau A., Van Snick J. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med. 1987 Mar 1;165(3):914–919. doi: 10.1084/jem.165.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Snick J., Cayphas S., Szikora J. P., Renauld J. C., Van Roost E., Boon T., Simpson R. J. cDNA cloning of murine interleukin-HP1: homology with human interleukin 6. Eur J Immunol. 1988 Feb;18(2):193–197. doi: 10.1002/eji.1830180202. [DOI] [PubMed] [Google Scholar]
- Van Snick J., Cayphas S., Vink A., Uyttenhove C., Coulie P. G., Rubira M. R., Simpson R. J. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679–9683. doi: 10.1073/pnas.83.24.9679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Snick J., Vink A., Cayphas S., Uyttenhove C. Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas. J Exp Med. 1987 Mar 1;165(3):641–649. doi: 10.1084/jem.165.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zilberstein A., Ruggieri R., Korn J. H., Revel M. Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J. 1986 Oct;5(10):2529–2537. doi: 10.1002/j.1460-2075.1986.tb04531.x. [DOI] [PMC free article] [PubMed] [Google Scholar]