Soluble CD16/FcγRIII Induces Maturation of Dendritic Cells and Production of Several Cytokines Including IL-12

  • H. de la Salle
  • J. Galon
  • H. Bausinger
  • D. Spehner
  • A. Bohbot
  • J. Cohen
  • J. -P. Cazenave
  • W. -H. Fridman
  • C. Sautés
  • D. Hanau
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)

Abstract

FcγRIII (CD16), a low affinity FcR which binds IgG-containing immune-complexes, exists under membrane-associated forms and under a soluble form (sFcγRIII). The latter, present in biological fluids (serum, saliva), is generated by proteolytic cleavage of the two membrane-associated FcγRIII isoforms, FcγRIII-A (expressed by macrophages and NK cells) and FcγRIII-B (expressed exclusively by neutrophils). Herein we demonstrate that dendritic cells (DCs), generated by culturing monocytes with GM-CSF and IL-4, bind biotinylated recombinant sFcγRIII. This binding is specific and involves the complement receptor CR3 (CD11b/CD18) and CR4 (CD11c/CD18). Indeed, preincubation of DCs with anti-CD11b and anti-CD11c mAbs decreased by 52% and 62% respectively the binding with sFcγRIII. Moreover, electron microscopy showed that binding of gold-labeled sFcγRIII to DCs maintained at 4°C occured within clathrin-coated pits. Once internalized, at 37°C, sFcγRIII entered the endocytic pathway and reached the MHC class II compartments. Furthemore, DCs incubated for 48 h with multivalent sFcγRIII expressed increased levels of CD40, CD80, CD86, CD54, CD58, HLA class I and class II molecules and decreased levels of CD23 and CD32. These effects result in an increased capacity of DCs to trigger proliferative responses by CD4+ CD45RA+ allogeneic T cells. RT-PCR amplification demonstrated that incubation of DCs for 20 h in the presence of multivalent sFcγRIII induced the appearance of GM-CSF and IL-12 p40 mRNA. Among the cytokines constitutively expressed, IL-lβ and IL-8 were strongly up-regulated whereas IL-6 and IL-12 p35 mRNA were increased to a lesser extent and the expression of MIP-lα mRNA remained constant. Finally, ELISA tests demonstrated that DCs incubated with multivalent sFcγRIII secreted the cytokines IL-1β, IL-6, IL-8, GM-CSF and IL-12 p75. Thus, while becoming internalized sFcγRIII could affect the capacity of DCs to present antigens and, via the induction of accessory molecules and the release of the IL-12 p75 protein, could initiate Thl type immune response.

Keywords

Endocytic Pathway Type Immune Response Induce Maturation Counterflow Centrifugation Elutriation Recombinant sCD16 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • H. de la Salle
    • 1
  • J. Galon
    • 3
  • H. Bausinger
    • 1
  • D. Spehner
    • 1
  • A. Bohbot
    • 4
  • J. Cohen
    • 5
  • J. -P. Cazenave
    • 2
  • W. -H. Fridman
    • 3
  • C. Sautés
    • 3
  • D. Hanau
    • 1
  1. 1.CJF 94-03 INSERMStrasbourgFrance
  2. 2.U. 311, E.T.S. INSERMStrasbourgFrance
  3. 3.INSERM U. 255Institut CurieParisFrance
  4. 4.Service d’Onco-HématologieHôpital de HautepierreStrasbourgFrance
  5. 5.Laboratoire d’ImmunologieHôpital Robert DebréReimsFrance

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