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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Jul;89(1):148–153. doi: 10.1111/j.1365-2249.1992.tb06894.x

IL-6 enhances the generation of cytolytic T lymphocytes in the allogeneic mixed leucocyte reaction.

J E Ming 1, R M Steinman 1, A Granelli-Piperno 1
PMCID: PMC1554396  PMID: 1385765

Abstract

Cytolytic T lymphocytes (CTL) require soluble proteins termed lymphokines to develop lytic activity. In this report we have studied two of the lymphokines involved in the development of CTL during the allogeneic mixed leucocyte reaction (MLR). High doses of dendritic cells induced lytic activity from purified CD8+ cells in both the murine and human MLR. Under these conditions, IL-2 and IL-6 were endogenously produced and secreted. Antibodies to IL-2 or the IL-2 receptor blocked CTL formation; however, anti-IL-6 receptor antibodies only partially inhibited the response while anti-IL-6 antibodies were largely ineffective. When limiting numbers of antigen-presenting cells were used CTL failed to develop, and neither IL-2 nor IL-6 was secreted into the culture supernatant. Although the addition of IL-6 to such cultures was ineffective in generating CTL, the combination of IL-2 and IL-6 resulted in a 4-5-fold increase in lytic activity over that of IL-2 alone. We conclude that in the allogeneic MLR, IL-2 and IL-6 contribute to the generation of lytically active CD8+ cells, and the effect of IL-6 is evident when the dose of antigen-presenting cell is limited.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Crowley M., Inaba K., Witmer-Pack M., Steinman R. M. The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. Cell Immunol. 1989 Jan;118(1):108–125. doi: 10.1016/0008-8749(89)90361-4. [DOI] [PubMed] [Google Scholar]
  2. Freudenthal P. S., Steinman R. M. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7698–7702. doi: 10.1073/pnas.87.19.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Hirata Y., Taga T., Hibi M., Nakano N., Hirano T., Kishimoto T. Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies. J Immunol. 1989 Nov 1;143(9):2900–2906. [PubMed] [Google Scholar]
  5. Holsti M. A., Raulet D. H. IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells. J Immunol. 1989 Oct 15;143(8):2514–2519. [PubMed] [Google Scholar]
  6. Houssiau F. A., Coulie P. G., Olive D., Van Snick J. Synergistic activation of human T cells by interleukin 1 and interleukin 6. Eur J Immunol. 1988 Apr;18(4):653–656. doi: 10.1002/eji.1830180427. [DOI] [PubMed] [Google Scholar]
  7. Houssiau F. A., Coulie P. G., Van Snick J. Distinct roles of IL-1 and IL-6 in human T cell activation. J Immunol. 1989 Oct 15;143(8):2520–2524. [PubMed] [Google Scholar]
  8. Inaba K., Young J. W., Steinman R. M. Direct activation of CD8+ cytotoxic T lymphocytes by dendritic cells. J Exp Med. 1987 Jul 1;166(1):182–194. doi: 10.1084/jem.166.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lorré K., Van Damme J., Verwilghen J., Baroja M. L., Ceuppens J. L. IL-6 is an accessory signal in the alternative CD2-mediated pathway of T cell activation. J Immunol. 1990 Jun 15;144(12):4681–4687. [PubMed] [Google Scholar]
  10. Lotz M., Jirik F., Kabouridis P., Tsoukas C., Hirano T., Kishimoto T., Carson D. A. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988 Mar 1;167(3):1253–1258. doi: 10.1084/jem.167.3.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. May L. T., Ghrayeb J., Santhanam U., Tatter S. B., Sthoeger Z., Helfgott D. C., Chiorazzi N., Grieninger G., Sehgal P. B. Synthesis and secretion of multiple forms of beta 2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes. J Biol Chem. 1988 Jun 5;263(16):7760–7766. [PubMed] [Google Scholar]
  12. Ming J. E., Cernetti C., Steinman R. M., Granelli-Piperno A. Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium. J Mol Cell Immunol. 1989;4(4):203–212. [PubMed] [Google Scholar]
  13. Ming J. E., Granelli-Piperno A. Distinctive features in the production of IL-6 by human T cells. Cell Immunol. 1990 Oct 15;130(2):437–445. doi: 10.1016/0008-8749(90)90285-y. [DOI] [PubMed] [Google Scholar]
  14. Naito K., Inaba K., Hirayama Y., Inaba-Miyama M., Sudo T., Muramatsu S. Macrophage factors which enhance the mixed leukocyte reaction initiated by dendritic cells. J Immunol. 1989 Mar 15;142(6):1834–1839. [PubMed] [Google Scholar]
  15. Okada M., Kitahara M., Kishimoto S., Matsuda T., Hirano T., Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol. 1988 Sep 1;141(5):1543–1549. [PubMed] [Google Scholar]
  16. Renauld J. C., Vink A., Van Snick J. Accessory signals in murine cytolytic T cell responses. Dual requirement for IL-1 and IL-6. J Immunol. 1989 Sep 15;143(6):1894–1898. [PubMed] [Google Scholar]
  17. Rosenberg S. A., Packard B. S., Aebersold P. M., Solomon D., Topalian S. L., Toy S. T., Simon P., Lotze M. T., Yang J. C., Seipp C. A. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988 Dec 22;319(25):1676–1680. doi: 10.1056/NEJM198812223192527. [DOI] [PubMed] [Google Scholar]
  18. Takai Y., Wong G. G., Clark S. C., Burakoff S. J., Herrmann S. H. B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol. 1988 Jan 15;140(2):508–512. [PubMed] [Google Scholar]
  19. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  20. Uyttenhove C., Coulie P. G., Van Snick J. T cell growth and differentiation induced by interleukin-HP1/IL-6, the murine hybridoma/plasmacytoma growth factor. J Exp Med. 1988 Apr 1;167(4):1417–1427. doi: 10.1084/jem.167.4.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Vink A., Uyttenhove C., Wauters P., Van Snick J. Accessory factors involved in murine T cell activation. Distinct roles of interleukin 6, interleukin 1 and tumor necrosis factor. Eur J Immunol. 1990 Jan;20(1):1–6. doi: 10.1002/eji.1830200102. [DOI] [PubMed] [Google Scholar]
  23. Young J. W., Steinman R. M. Dendritic cells stimulate primary human cytolytic lymphocyte responses in the absence of CD4+ helper T cells. J Exp Med. 1990 Apr 1;171(4):1315–1332. doi: 10.1084/jem.171.4.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]

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