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Immunology logoLink to Immunology
. 1989 Jul;67(3):290–297.

Human dendritic cells stimulate allogeneic T cells in the absence of IL-1.

J L McKenzie 1, T C Prickett 1, D N Hart 1
PMCID: PMC1385342  PMID: 2527194

Abstract

Dendritic cells (DC), which express high-density HLA class II molecules, stimulate strong primary allogeneic T-cell responses via an interaction of the T-cell receptor with major histocompatibility complex (MHC) antigens (signal 1). It is not yet clear whether they also provide a second stimulus to the responding T cell in the form of the cytokine interleukin-1 (IL-1). To clarify this point, the ability of purified human tonsil DC to produce IL-1 and to stimulate allogeneic T cells was tested. No intracellular IL-1 alpha or beta was identified in DC comparable to that readily demonstrated in monocytes, and IL-1 release from lipopolysaccharide (LPS)-stimulated DC was not detected in either a biological assay for IL-1 or an ELISA assay for IL-1 beta. Furthermore, strong stimulation of allogeneic T lymphocytes by DC in the mixed leucocyte reaction (MLR) was noted to occur in the absence of IL-1 production, and this stimulation was not inhibited by polyclonal antisera to IL-1 alpha and IL-1 beta, which were known to inhibit IL-1-mediated thymocyte proliferation. Other HLA-class II-positive cell populations, namely peripheral blood monocytes and B cells, purified by methods which avoided DC contamination, were unable to stimulate allogeneic T cells with or without supplementary IL-1. We conclude that DC are very effective stimulators of T lymphocytes and that IL-1 is not required as a second signal for allogeneic T-cell responses.

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Selected References

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

  1. Aaron S. T cell blast stimulation of MLR: role of interleukin 1 and interleukin 2. Clin Exp Immunol. 1988 Jan;71(1):171–176. [PMC free article] [PubMed] [Google Scholar]
  2. Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
  3. 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]
  4. Bjercke S., Gaudernack G. Dendritic cells and monocytes as accessory cells in T-cell responses in man. II. Function as antigen-presenting cells. Scand J Immunol. 1985 May;21(5):501–508. doi: 10.1111/j.1365-3083.1985.tb01839.x. [DOI] [PubMed] [Google Scholar]
  5. Conlon P. J., Grabstein K. H., Alpert A., Prickett K. S., Hopp T. P., Gillis S. Localization of human mononuclear cell interleukin 1. J Immunol. 1987 Jul 1;139(1):98–102. [PubMed] [Google Scholar]
  6. Cosentino L. M., Cathcart M. K. A multi-step isolation scheme for obtaining CD16+ human natural killer cells. J Immunol Methods. 1987 Nov 5;103(2):195–204. doi: 10.1016/0022-1759(87)90290-0. [DOI] [PubMed] [Google Scholar]
  7. Crow M. K., Kunkel H. G. Human dendritic cells: major stimulators of the autologous and allogeneic mixed leucocyte reactions. Clin Exp Immunol. 1982 Aug;49(2):338–346. [PMC free article] [PubMed] [Google Scholar]
  8. Dower S. K., Kronheim S. R., March C. J., Conlon P. J., Hopp T. P., Gillis S., Urdal D. L. Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med. 1985 Aug 1;162(2):501–515. doi: 10.1084/jem.162.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Doyle C., Strominger J. L. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987 Nov 19;330(6145):256–259. doi: 10.1038/330256a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Gay D., Maddon P., Sekaly R., Talle M. A., Godfrey M., Long E., Goldstein G., Chess L., Axel R., Kappler J. Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature. 1987 Aug 13;328(6131):626–629. doi: 10.1038/328626a0. [DOI] [PubMed] [Google Scholar]
  12. Gearing A. J., Johnstone A. P., Thorpe R. Production and assay of the interleukins. J Immunol Methods. 1985 Oct 24;83(1):1–27. doi: 10.1016/0022-1759(85)90053-5. [DOI] [PubMed] [Google Scholar]
  13. Gillis S., Mizel S. B. T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1133–1137. doi: 10.1073/pnas.78.2.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goto M., Sasano M., Yamanaka H., Miyasaka N., Kamatani N., Inoue K., Nishioka K., Miyamoto T. Spontaneous production of an interleukin 1-like factor by cloned rheumatoid synovial cells in long-term culture. J Clin Invest. 1987 Sep;80(3):786–796. doi: 10.1172/JCI113135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hagiwara H., Huang H. J., Arai N., Herzenberg L. A., Arai K., Zlotnik A. Interleukin 1 modulates messenger RNA levels of lymphokines and of other molecules associated with T cell activation in the T cell lymphoma LBRM33-1A5. J Immunol. 1987 Apr 15;138(8):2514–2519. [PubMed] [Google Scholar]
  16. Haq A. U., Mayernik D. G., Orosz C., Rinehart J. J. Interleukin 1 secretion is not required for human macrophage support of T-cell proliferation. Cell Immunol. 1984 Sep;87(2):517–527. doi: 10.1016/0008-8749(84)90020-0. [DOI] [PubMed] [Google Scholar]
  17. Hart D. N., Fabre J. W. Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med. 1981 Aug 1;154(2):347–361. doi: 10.1084/jem.154.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hart D. N., Fuggle S. V., Williams K. A., Fabre J. W., Ting A., Morris P. J. Localization of HLA-ABC and DR antigens in human kidney. Transplantation. 1981 Jun;31(6):428–433. doi: 10.1097/00007890-198106000-00005. [DOI] [PubMed] [Google Scholar]
  19. Hart D. N., McKenzie J. L. Isolation and characterization of human tonsil dendritic cells. J Exp Med. 1988 Jul 1;168(1):157–170. doi: 10.1084/jem.168.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Inaba K., Witmer M. D., Steinman R. M. Clustering of dendritic cells, helper T lymphocytes, and histocompatible B cells during primary antibody responses in vitro. J Exp Med. 1984 Sep 1;160(3):858–876. doi: 10.1084/jem.160.3.858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Lepe-Zuniga J. L., Gery I. Production of intra- and extracellular interleukin-1 (IL-1) by human monocytes. Clin Immunol Immunopathol. 1984 May;31(2):222–230. doi: 10.1016/0090-1229(84)90242-3. [DOI] [PubMed] [Google Scholar]
  25. Maizel A. L., Mehta S. R., Ford R. J., Lachman L. B. Effect of interleukin 1 on human thymocytes and purified human T cells. J Exp Med. 1981 Feb 1;153(2):470–475. doi: 10.1084/jem.153.2.470. [DOI] [PMC free article] [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. Nagelkerken L. M., van Breda Vriesman P. J. Membrane-associated IL 1-like activity on rat dendritic cells. J Immunol. 1986 Mar 15;136(6):2164–2170. [PubMed] [Google Scholar]
  28. Paetkau V., Mills G., Gerhart S., Monticone V. Proliferation of murine thymic lymphocytes in vitro is mediated by the concanavalin A-induced release of a lymphokine (costimulator). J Immunol. 1976 Oct;117(4):1320–1324. [PubMed] [Google Scholar]
  29. Prickett T. C., McKenzie J. L., Hart D. N. Characterization of interstitial dendritic cells in human liver. Transplantation. 1988 Nov;46(5):754–761. doi: 10.1097/00007890-198811000-00024. [DOI] [PubMed] [Google Scholar]
  30. Sauder D. N., Dinarello C. A., Morhenn V. B. Langerhans cell production of interleukin-1. J Invest Dermatol. 1984 Jun;82(6):605–607. doi: 10.1111/1523-1747.ep12261439. [DOI] [PubMed] [Google Scholar]
  31. Scala G., Allavena P., Djeu J. Y., Kasahara T., Ortaldo J. R., Herberman R. B., Oppenheim J. J. Human large granular lymphocytes are potent producers of interleukin-1. Nature. 1984 May 3;309(5963):56–59. doi: 10.1038/309056a0. [DOI] [PubMed] [Google Scholar]
  32. Scala G., Oppenheim J. J. Antigen presentation by human monocytes: evidence for stimulant processing and requirement for interleukin 1. J Immunol. 1983 Sep;131(3):1160–1166. [PubMed] [Google Scholar]
  33. Shimada S., Caughman S. W., Sharrow S. O., Stephany D., Katz S. I. Enhanced antigen-presenting capacity of cultured Langerhans' cells is associated with markedly increased expression of Ia antigen. J Immunol. 1987 Oct 15;139(8):2551–2555. [PubMed] [Google Scholar]
  34. Shirakawa F., Tanaka Y., Ota T., Suzuki H., Eto S., Yamashita U. Expression of interleukin 1 receptors on human peripheral T cells. J Immunol. 1987 Jun 15;138(12):4243–4248. [PubMed] [Google Scholar]
  35. Steinman R. M. Cytokines amplify the function of accessory cells. Immunol Lett. 1988 Mar;17(3):197–202. doi: 10.1016/0165-2478(88)90028-4. [DOI] [PubMed] [Google Scholar]
  36. Steinman R. M., Gutchinov B., Witmer M. D., Nussenzweig M. C. Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J Exp Med. 1983 Feb 1;157(2):613–627. doi: 10.1084/jem.157.2.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ugolini V., Nunez G., Smith R. G., Stastny P., Capra J. D. Initial characterization of monoclonal antibodies against human monocytes. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6764–6768. doi: 10.1073/pnas.77.11.6764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Van Voorhis W. C., Hair L. S., Steinman R. M., Kaplan G. Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med. 1982 Apr 1;155(4):1172–1187. doi: 10.1084/jem.155.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Waalen K., Duff G. W., Førre O., Dickens E., Kvarnes L., Nuki G. Interleukin 1 activity produced by human rheumatoid and normal dendritic cells. Scand J Immunol. 1986 Mar;23(3):365–371. doi: 10.1111/j.1365-3083.1986.tb01977.x. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. 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]

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