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. 1987 Feb 1;165(2):515–530. doi: 10.1084/jem.165.2.515

Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells

PMCID: PMC2188514  PMID: 2950198

Abstract

The function of exogenous murine recombinant IL-1 alpha as a T lymphocyte-activating molecule was examined. IL-1 did not induce IL-2 release or responsiveness in purified T cells regardless of their state of activation: unprimed lymphocytes, freshly sensitized lymphocytes, or memory cells derived from the blasts. Nor did IL-1 synergize with mitogens, or with antigens, to stimulate proliferation. For example the combinations of IL-1 plus Ia+ peritoneal macrophages, or IL-1 plus Con A, were less than 5% as effective in triggering T cell growth as a low dose (1%) of dendritic cells. However, when IL-1 was added at the onset of culture, the response to limiting doses of dendritic cells was increased 3- to 10-fold in several systems: the syngeneic and allogeneic MLR, Con A- and periodate-induced polyclonal mitogenesis, and T-dependent antibody formation against foreign red cells. The amplifying effect of IL-1 could be obtained if the dendritic cells but not the responding lymphocytes were exposed to IL-1 before use as accessory cells. Optimal activation of dendritic cells required a dose of 5 U/ml (50 pM) and 18 h of exposure, and was not due to carryover of IL-1 into the lymphocyte culture. IL-2, IL-3, and cachectin/TNF did not amplify dendritic cell function, while IFN-gamma diminished it. The enhanced function of IL-1-treated dendritic cells was due to an enhanced clustering with helper T lymphocytes in the first day of the MLR response. Therefore IL-1 does not seem to act as an activating factor for most peripheral T lymphocytes. Instead, IL-1 enhances the function of accessory dendritic cells and represents the first molecule that has been shown to enhance the immune response at this critical level.

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Selected References

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  1. Austyn J. M., Steinman R. M., Weinstein D. E., Granelli-Piperno A., Palladino M. A. Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation. J Exp Med. 1983 Apr 1;157(4):1101–1115. doi: 10.1084/jem.157.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beutler B., Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. doi: 10.1038/320584a0. [DOI] [PubMed] [Google Scholar]
  3. De la Harpe J., Nathan C. F. A semi-automated micro-assay for H2O2 release by human blood monocytes and mouse peritoneal macrophages. J Immunol Methods. 1985 Apr 22;78(2):323–336. doi: 10.1016/0022-1759(85)90089-4. [DOI] [PubMed] [Google Scholar]
  4. Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
  5. Gery I., Gershon R. K., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Honig M. G., Hume R. I. Fluorescent carbocyanine dyes allow living neurons of identified origin to be studied in long-term cultures. J Cell Biol. 1986 Jul;103(1):171–187. doi: 10.1083/jcb.103.1.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Inaba K., Koide S., Steinman R. M. Properties of memory T lymphocytes isolated from the mixed leukocyte reaction. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7686–7690. doi: 10.1073/pnas.82.22.7686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Inaba K., Steinman R. M. Accessory cell-T lymphocyte interactions. Antigen-dependent and -independent clustering. J Exp Med. 1986 Feb 1;163(2):247–261. doi: 10.1084/jem.163.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Inaba K., Steinman R. M. Protein-specific helper T-lymphocyte formation initiated by dendritic cells. Science. 1985 Aug 2;229(4712):475–479. doi: 10.1126/science.3160115. [DOI] [PubMed] [Google Scholar]
  12. Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kasahara T., Mukaida N., Hatake K., Motoyoshi K., Kawai T., Shiori-Nakano K. Interleukin 1 (IL 1)-dependent lymphokine production by human leukemic T cell line HSB.2 subclones. J Immunol. 1985 Mar;134(3):1682–1689. [PubMed] [Google Scholar]
  14. Kaye J., Gillis S., Mizel S. B., Shevach E. M., Malek T. R., Dinarello C. A., Lachman L. B., Janeway C. A., Jr Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. J Immunol. 1984 Sep;133(3):1339–1345. [PubMed] [Google Scholar]
  15. Larsson E. L., Iscove N. N., Coutinho A. Two distinct factors are required for induction of T-cell growth. Nature. 1980 Feb 14;283(5748):664–666. doi: 10.1038/283664a0. [DOI] [PubMed] [Google Scholar]
  16. Lomedico P. T., Gubler U., Hellmann C. P., Dukovich M., Giri J. G., Pan Y. C., Collier K., Semionow R., Chua A. O., Mizel S. B. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. 1984 Nov 29-Dec 5Nature. 312(5993):458–462. doi: 10.1038/312458a0. [DOI] [PubMed] [Google Scholar]
  17. Luger T. A., Stadler B. M., Katz S. I., Oppenheim J. J. Epidermal cell (keratinocyte)-derived thymocyte-activating factor (ETAF). J Immunol. 1981 Oct;127(4):1493–1498. [PubMed] [Google Scholar]
  18. Luger T. A., Wirth U., Köck A. Epidermal cells synthesize a cytokine with interleukin 3-like properties. J Immunol. 1985 Feb;134(2):915–919. [PubMed] [Google Scholar]
  19. 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]
  20. Nussenzweig M. C., Steinman R. M. Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction. J Exp Med. 1980 May 1;151(5):1196–1212. doi: 10.1084/jem.151.5.1196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rao A., Mizel S. B., Cantor H. Disparate functional properties of two interleukin 1-responsive Ly-1+2- T cell clones: distinction of T cell growth factor and T cell-replacing factor activities. J Immunol. 1983 Apr;130(4):1743–1748. [PubMed] [Google Scholar]
  22. Ruff M. R., Gifford G. E. Purification and physico-chemical characterization of rabbit tumor necrosis factor. J Immunol. 1980 Oct;125(4):1671–1677. [PubMed] [Google Scholar]
  23. Schrader J. W., Battye F., Scollay R. Expression of Thy-1 antigen is not limited to T cells in cultures of mouse hemopoietic cells. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4161–4165. doi: 10.1073/pnas.79.13.4161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smith K. A., Gilbride K. J., Favata M. F. Lymphocyte activating factor promotes T-cell growth factor production by cloned murine lymphoma cells. Nature. 1980 Oct 30;287(5785):853–855. doi: 10.1038/287853a0. [DOI] [PubMed] [Google Scholar]
  26. Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steeg P. S., Moore R. N., Johnson H. M., Oppenheim J. J. Regulation of murine macrophage Ia antigen expression by a lymphokine with immune interferon activity. J Exp Med. 1982 Dec 1;156(6):1780–1793. doi: 10.1084/jem.156.6.1780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Steinman R. M., Kaplan G., Witmer M. D., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J Exp Med. 1979 Jan 1;149(1):1–16. doi: 10.1084/jem.149.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steinman R. M., Nogueira N., Witmer M. D., Tydings J. D., Mellman I. S. Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages. J Exp Med. 1980 Nov 1;152(5):1248–1261. doi: 10.1084/jem.152.5.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wright S. D., Silverstein S. C. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med. 1982 Oct 1;156(4):1149–1164. doi: 10.1084/jem.156.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]

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