Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Sep;93(3):471–478. doi: 10.1111/j.1365-2249.1993.tb08203.x

Interaction of IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in human T cells activated by murine antigens.

S Panzer 1, M Madden 1, K Matsuki 1
PMCID: PMC1554907  PMID: 8370177

Abstract

We used a mixed leucocyte culture between human T cells and irradiated murine splenocytes which allowed us to distinguish between cytokine production from the responder and stimulator cells by the use of species-specific assays for mRNA up-regulation. Using this model of T cell activation by antigen, we studied the effects of human antigen-presenting cell-derived cytokines IL-1 beta, IL-6 and TNF-alpha on the activation of human T cell subsets. We show in this system that exogenously added IL-1 beta, IL-6 and TNF-alpha induces IL-2 receptor (R) up-regulation and IL-2 production, and proliferation by both CD4+ and CD8+ cells. The addition of IL-1 beta induces IL-6 mRNA, and anti-IL-1 antibodies or an IL-1R antagonist protein completely suppresses IL-6 and TNF-alpha supported proliferation. Similarly, addition of IL-6 or TNF-alpha induces up-regulation of IL-1 beta mRNA. However, anti-IL-6 and anti-IL-6R antibodies only partially block proliferation supported by IL-1 beta. These findings suggest that IL-6 and TNF-alpha will induce IL-2R up-regulation/IL-2 secretion via the induction of IL-1 beta production.

Full text

PDF
471

Images in this article

Selected References

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

  1. Akira S., Hirano T., Taga T., Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990 Aug;4(11):2860–2867. [PubMed] [Google Scholar]
  2. Alter B. J., Bach F. H. Cellular basis of the proliferative response of human T cells to mouse xenoantigens. J Exp Med. 1990 Jan 1;171(1):333–338. doi: 10.1084/jem.171.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bach F. H., Geller R. L., Nelson P. J., Panzer S., Gromo G., Benfield M. R., Inverardi L., Podack E. R., Witson J. C., Houchins J. P. A "minimal signal-stepwise activation" analysis of functional maturation of T lymphocytes. Immunol Rev. 1989 Oct;111:35–57. doi: 10.1111/j.1600-065x.1989.tb00541.x. [DOI] [PubMed] [Google Scholar]
  4. Baroja M. L., Ceuppens J. L., Van Damme J., Billiau A. Cooperation between an anti-T cell (anti-CD28) monoclonal antibody and monocyte-produced IL-6 in the induction of T cell responsiveness to IL-2. J Immunol. 1988 Sep 1;141(5):1502–1507. [PubMed] [Google Scholar]
  5. Brenner C. A., Tam A. W., Nelson P. A., Engleman E. G., Suzuki N., Fry K. E., Larrick J. W. Message amplification phenotyping (MAPPing): a technique to simultaneously measure multiple mRNAs from small numbers of cells. Biotechniques. 1989 Nov-Dec;7(10):1096–1103. [PubMed] [Google Scholar]
  6. Brunswick M., Lake P. Functional interactions of human and murine lymphoid cells. I. Analysis of primary and secondary responses. Cell Immunol. 1986 Dec;103(2):441–454. doi: 10.1016/0008-8749(86)90104-8. [DOI] [PubMed] [Google Scholar]
  7. Carter D. B., Deibel M. R., Jr, Dunn C. J., Tomich C. S., Laborde A. L., Slightom J. L., Berger A. E., Bienkowski M. J., Sun F. F., McEwan R. N. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature. 1990 Apr 12;344(6267):633–638. doi: 10.1038/344633a0. [DOI] [PubMed] [Google Scholar]
  8. Ceuppens J. L., Baroja M. L., Lorre K., Van Damme J., Billiau A. Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal. J Immunol. 1988 Dec 1;141(11):3868–3874. [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Crabtree G. R. Contingent genetic regulatory events in T lymphocyte activation. Science. 1989 Jan 20;243(4889):355–361. doi: 10.1126/science.2783497. [DOI] [PubMed] [Google Scholar]
  11. Davis L., Lipsky P. E. Signals involved in T cell activation. II. Distinct roles of intact accessory cells, phorbol esters, and interleukin 1 in activation and cell cycle progression of resting T lymphocytes. J Immunol. 1986 May 15;136(10):3588–3596. [PubMed] [Google Scholar]
  12. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Endler-Jobst B., Schraven B., Hutmacher B., Meuer S. C. Human T cell responses to IL-1 and IL-6 are dependent on signals mediated through CD2. J Immunol. 1991 Mar 15;146(6):1736–1742. [PubMed] [Google Scholar]
  14. 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]
  15. Golding H., Singer A. Role of accessory cell processing and presentation of shed H-2 alloantigens in allospecific cytotoxic T lymphocyte responses. J Immunol. 1984 Aug;133(2):597–605. [PubMed] [Google Scholar]
  16. Hackett R. J., Davis L. S., Lipsky P. E. Comparative effects of tumor necrosis factor-alpha and IL-1 beta on mitogen-induced T cell activation. J Immunol. 1988 Apr 15;140(8):2639–2644. [PubMed] [Google Scholar]
  17. Horii Y., Muraguchi A., Suematsu S., Matsuda T., Yoshizaki K., Hirano T., Kishimoto T. Regulation of BSF-2/IL-6 production by human mononuclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol. 1988 Sep 1;141(5):1529–1535. [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Kruisbeek A. M., Andrysiak P. M., Singer A. Self recognition of accessory cell Ia determinants is required for the in vitro generation of hapten-specific cytotoxic T lymphocyte responses. J Immunol. 1983 Oct;131(4):1650–1655. [PubMed] [Google Scholar]
  21. Le J. M., Fredrickson G., Reis L. F., Diamantstein T., Hirano T., Kishimoto T., Vilcek J. Interleukin 2-dependent and interleukin 2-independent pathways of regulation of thymocyte function by interleukin 6. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8643–8647. doi: 10.1073/pnas.85.22.8643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lindahl K. F., Bach F. H. Genetic and cellular aspects of xenogeneic mixed leukocyte culture reaction. J Exp Med. 1976 Aug 1;144(2):305–318. doi: 10.1084/jem.144.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Lowenthal J. W., MacDonald H. R. Expression of interleukin 1 receptors is restricted to the L3T4+ subset of mature T lymphocytes. J Immunol. 1987 Jan 1;138(1):1–3. [PubMed] [Google Scholar]
  26. Mizel S. B. Interleukin 1 and T cell activation. Immunol Rev. 1982;63:51–72. doi: 10.1111/j.1600-065x.1982.tb00411.x. [DOI] [PubMed] [Google Scholar]
  27. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Panzer S., Geller R. L., Bach F. H. Purified human T cells stimulated with cross-linked anti-CD3 monoclonal antibody OKT3: rIL-1 is a co-stimulatory factor for CD4+CD29+CD45RA- T cells. Scand J Immunol. 1990 Oct;32(4):359–371. doi: 10.1111/j.1365-3083.1990.tb02930.x. [DOI] [PubMed] [Google Scholar]
  29. Scheurich P., Thoma B., Ucer U., Pfizenmaier K. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol. 1987 Mar 15;138(6):1786–1790. [PubMed] [Google Scholar]
  30. Shalaby M. R., Espevik T., Rice G. C., Ammann A. J., Figari I. S., Ranges G. E., Palladino M. A., Jr The involvement of human tumor necrosis factors-alpha and -beta in the mixed lymphocyte reaction. J Immunol. 1988 Jul 15;141(2):499–503. [PubMed] [Google Scholar]
  31. Singer A., Kruisbeek A. M., Andrysiak P. M. T cell-accessory cell interactions that initiate allospecific cytotoxic T lymphocyte responses: existence of both Ia-restricted and Ia-unrestricted cellular interaction pathways. J Immunol. 1984 May;132(5):2199–2209. [PubMed] [Google Scholar]
  32. Tosato G., Miller J., Marti G., Pike S. E. Accessory function of interleukin-1 and interleukin-6: preferential costimulation of T4 positive lymphocytes. Blood. 1990 Feb 15;75(4):922–930. [PubMed] [Google Scholar]
  33. Tosato G., Pike S. E. Interferon-beta 2/interleukin 6 is a co-stimulant for human T lymphocytes. J Immunol. 1988 Sep 1;141(5):1556–1562. [PubMed] [Google Scholar]
  34. Turner M., Chantry D., Buchan G., Barrett K., Feldmann M. Regulation of expression of human IL-1 alpha and IL-1 beta genes. J Immunol. 1989 Dec 1;143(11):3556–3561. [PubMed] [Google Scholar]
  35. 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]
  36. 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]
  37. 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]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES