Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Mar 1;169(3):1121–1136. doi: 10.1084/jem.169.3.1121

Interleukin 1 production during accessory cell-dependent mitogenesis of T lymphocytes

PMCID: PMC2189278  PMID: 2522495

Abstract

We have studied the control and significance of IL-1 production in human leukocyte cultures during accessory cell-dependent, T lymphocyte mitogenesis using sensitive bioassays and immunolabeling techniques. In primary antigen-dependent systems like the MLR, IL-1 production was not detected in accessory cells (monocytes, dendritic cells) or T cells, suggesting that it is not an early product in these responses. However, monocytes could be induced to make IL-1 after interacting with sensitized antigen-specific T cells. Both alloreactive T cell clones or freshly prepared lymphoblasts induced IL-1 provided the monocytes carried the HLA-DR antigens to which the T cells were initially sensitized. Even in these circumstances, dendritic cells and B cells failed to make IL-1. The mechanism whereby activated T cells induce IL- 1 in monocytes was explored. Supernatants from cocultures of monocytes and T cells or several recombinant cytokines induced little or no IL-1. A more potent antigen independent pathway of IL-1 induction was identified. IL-1 could be induced in third-party HLA-DR nonspecific monocytes in cocultures of alloreactive T cell clones or blasts and HLA- DR-specific dendritic cells. The induction was factor independent since dendritic cells and T blasts placed in a chamber separate from third- party monocytes by a semipermeable membrane did not induce monocyte IL- 1. These results suggest that a cell contact mechanism rather than an IL-1-inducing factor leads to IL-1 production. The role of IL-1 in T cell proliferation was tested with a polyclonal anti-IL-1 antibody. The antibody failed to block the proliferation of primary T cells, or alloreactive T cell clones and blasts stimulated with HLA-specific monocytes or dendritic cells, even though IL-1 in the medium was neutralized.

Full Text

The Full Text of this article is available as a PDF (1,014.7 KB).

Selected References

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

  1. Bayne E. K., Rupp E. A., Limjuco G., Chin J., Schmidt J. A. Immunocytochemical detection of interleukin 1 within stimulated human monocytes. J Exp Med. 1986 May 1;163(5):1267–1280. doi: 10.1084/jem.163.5.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bhardwaj N., Lau L. L., Rivelis M., Steinman R. M. Interleukin-1 production by mononuclear cells from rheumatoid synovial effusions. Cell Immunol. 1988 Jul;114(2):405–423. doi: 10.1016/0008-8749(88)90332-2. [DOI] [PubMed] [Google Scholar]
  3. Defrance T., Aubry J. P., Rousset F., Vanbervliet B., Bonnefoy J. Y., Arai N., Takebe Y., Yokota T., Lee F., Arai K. Human recombinant interleukin 4 induces Fc epsilon receptors (CD23) on normal human B lymphocytes. J Exp Med. 1987 Jun 1;165(6):1459–1467. doi: 10.1084/jem.165.6.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dustin M. L., Singer K. H., Tuck D. T., Springer T. A. Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J Exp Med. 1988 Apr 1;167(4):1323–1340. doi: 10.1084/jem.167.4.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Flechner E. R., Freudenthal P. S., Kaplan G., Steinman R. M. Antigen-specific T lymphocytes efficiently cluster with dendritic cells in the human primary mixed-leukocyte reaction. Cell Immunol. 1988 Jan;111(1):183–195. doi: 10.1016/0008-8749(88)90062-7. [DOI] [PubMed] [Google Scholar]
  6. Friedman S. M., Green A., Russo C., Posnett D. N., Diffley D., Crow M. K. Amplification of altered self-reactive cytolytic T lymphocyte responses by cloned, allospecific human Th cells. J Clin Invest. 1988 Nov;82(5):1722–1730. doi: 10.1172/JCI113786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Ho S. N., Abraham R. T., Nilson A., Handwerger B. S., McKean D. J. Interleukin 1-mediated activation of interleukin 4 (IL 4)-producing T lymphocytes. Proliferation by IL 4-dependent and IL 4-independent mechanisms. J Immunol. 1987 Sep 1;139(5):1532–1540. [PubMed] [Google Scholar]
  9. Inaba K., Witmer-Pack M. D., Inaba M., Muramatsu S., Steinman R. M. The function of Ia+ dendritic cells and Ia- dendritic cell precursors in thymocyte mitogenesis to lectin and lectin plus interleukin 1. J Exp Med. 1988 Jan 1;167(1):149–162. doi: 10.1084/jem.167.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kohase M., May L. T., Tamm I., Vilcek J., Sehgal P. B. A cytokine network in human diploid fibroblasts: interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol Cell Biol. 1987 Jan;7(1):273–280. doi: 10.1128/mcb.7.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Koide S. L., Inaba K., Steinman R. M. Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells. J Exp Med. 1987 Feb 1;165(2):515–530. doi: 10.1084/jem.165.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koide S., Steinman R. M. Induction of interleukin 1 alpha mRNA during the antigen-dependent interaction of sensitized T lymphoblasts with macrophages. J Exp Med. 1988 Jul 1;168(1):409–416. doi: 10.1084/jem.168.1.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koide S., Steinman R. M. Induction of murine interleukin 1: stimuli and responsive primary cells. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3802–3806. doi: 10.1073/pnas.84.11.3802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kupper T. S., Ballard D. W., Chua A. O., McGuire J. S., Flood P. M., Horowitz M. C., Langdon R., Lightfoot L., Gubler U. Human keratinocytes contain mRNA indistinguishable from monocyte interleukin 1 alpha and beta mRNA. Keratinocyte epidermal cell-derived thymocyte-activating factor is identical to interleukin 1. J Exp Med. 1986 Dec 1;164(6):2095–2100. doi: 10.1084/jem.164.6.2095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kurt-Jones E. A., Hamberg S., Ohara J., Paul W. E., Abbas A. K. Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. J Exp Med. 1987 Dec 1;166(6):1774–1787. doi: 10.1084/jem.166.6.1774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Limjuco G., Galuska S., Chin J., Cameron P., Boger J., Schmidt J. A. Antibodies of predetermined specificity to the major charged species of human interleukin 1. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3972–3976. doi: 10.1073/pnas.83.11.3972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Schwab R., Crow M. K., Russo C., Weksler M. E. Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. J Immunol. 1985 Sep;135(3):1714–1718. [PubMed] [Google Scholar]
  19. Takacs L., Berzofsky J. A., York-Jolley J., Akahoshi T., Blasi E., Durum S. K. IL 1 induction by murine T cell clones: detection of an IL 1-inducing lymphokine. J Immunol. 1987 Apr 1;138(7):2124–2131. [PubMed] [Google Scholar]
  20. Tartakovsky B., Kovacs E. J., Takacs L., Durum S. K. T cell clone producing an IL 1-like activity after stimulation by antigen-presenting B cells. J Immunol. 1986 Jul 1;137(1):160–166. [PubMed] [Google Scholar]
  21. 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]
  22. Van Voorhis W. C., Steinman R. M., Hair L. S., Luban J., Witmer M. D., Koide S., Cohn Z. A. Specific antimononuclear phagocyte monoclonal antibodies. Application to the purification of dendritic cells and the tissue localization of macrophages. J Exp Med. 1983 Jul 1;158(1):126–145. doi: 10.1084/jem.158.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Weaver C. T., Unanue E. R. T cell induction of membrane IL 1 on macrophages. J Immunol. 1986 Dec 15;137(12):3868–3873. [PubMed] [Google Scholar]
  24. Williams J. M., Deloria D., Hansen J. A., Dinarello C. A., Loertscher R., Shapiro H. M., Strom T. B. The events of primary T cell activation can be staged by use of Sepharose-bound anti-T3 (64.1) monoclonal antibody and purified interleukin 1. J Immunol. 1985 Oct;135(4):2249–2255. [PubMed] [Google Scholar]
  25. Young J. W., Steinman R. M. Accessory cell requirements for the mixed-leukocyte reaction and polyclonal mitogens, as studied with a new technique for enriching blood dendritic cells. Cell Immunol. 1988 Jan;111(1):167–182. doi: 10.1016/0008-8749(88)90061-5. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES