Increased production of pro-inflammatory cytokines and enhanced T cell responses after activation of human dendritic cells with IL-1 and CD40 ligand.

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  • Author(s): Wesa A;Wesa A; Galy A
  • Source:
    BMC immunology [BMC Immunol] 2002 Oct 18; Vol. 3, pp. 14. Date of Electronic Publication: 2002 Oct 18.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100966980 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2172 (Electronic) Linking ISSN: 14712172 NLM ISO Abbreviation: BMC Immunol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2000-
    • Subject Terms:
      CD40 Ligand/*pharmacology ; Cytokines/*biosynthesis ; Dendritic Cells/*drug effects ; Interleukin-1/*pharmacology ; T-Lymphocytes/*immunology; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; CD40 Antigens/immunology ; CD40 Ligand/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Cytokines/immunology ; Dendritic Cells/metabolism ; Gene Expression ; Humans ; In Vitro Techniques ; Interferon-gamma/metabolism ; Interleukin-1/immunology ; Interleukin-10/biosynthesis ; Interleukin-10/immunology ; Interleukin-12/biosynthesis ; Interleukin-12/metabolism ; Interleukin-23 ; Interleukin-23 Subunit p19 ; Interleukin-6/biosynthesis ; Interleukins/biosynthesis ; Interleukins/metabolism ; T-Lymphocytes/cytology
    • Abstract:
      Background: Various microbial, inflammatory and immune signals regulate the activation of dendritic cells (DC), determining their ability to interact with naïve T cells and to produce cytokines that direct T cell development. In particular, CD40L and IL-1 cooperatively activate DC to secrete high levels of IL-12. The immuno-stimulatory capacity of such DC is otherwise not well-defined prompting further characterization of the effects of IL-1 and family members on DC activation in comparison with other pro-inflammatory stimuli.
      Results: Human DC co-activated in vitro by CD40L and IL-1beta expressed numerous cytokine genes including IL-12beta, IL-23 p19, IL-1beta, IL-1alpha, IL-1Ra, IL-10, IL-6, IL-18 and IFN-gamma. These DC produced high levels of IL-12 protein and appeared capable of producing IFN-gamma. Potent CD4+ and CD8+ T cell-stimulatory properties were acquired by DC under conditions that also induced IL-12. Notably, these DC induced rapid differentiation of fluMP-specific CD8+ T cells. Molecules related to IL-1beta, like IL-1alpha, co-induced IL-12 secretion whereas IL-18 did not. Conversely, the inhibitor IL-1Ra, produced endogenously by DC curtailed IL-12 production in response to CD40L.
      Conclusions: IL-1 and IL-1Ra play a biologically-relevant role in the positive and negative regulation of DC activation. In conjunction with CD40L, IL-1 sends a powerful activation signal to DC that could be distinguished from other modes of activation. This signal enables the production of pro-inflammatory cytokines by DC, and enhances the differentiation of naïve T cells into effectors of type-1 cellular immune responses.
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    • Grant Information:
      R01 CA082884 United States CA NCI NIH HHS; T32 CA009531 United States CA NCI NIH HHS; R01 CA82884-03 United States CA NCI NIH HHS; T32 CA09531 United States CA NCI NIH HHS
    • Accession Number:
      0 (CD40 Antigens)
      0 (Cytokines)
      0 (IL23A protein, human)
      0 (Interleukin-1)
      0 (Interleukin-23)
      0 (Interleukin-23 Subunit p19)
      0 (Interleukin-6)
      0 (Interleukins)
      130068-27-8 (Interleukin-10)
      147205-72-9 (CD40 Ligand)
      187348-17-0 (Interleukin-12)
      82115-62-6 (Interferon-gamma)
    • Publication Date:
      Date Created: 20021019 Date Completed: 20031203 Latest Revision: 20191106
    • Publication Date:
      20221213
    • Accession Number:
      PMC134468
    • Accession Number:
      10.1186/1471-2172-3-14
    • Accession Number:
      12385649