IL-10 alters DC function via modulation of cell surface molecules resulting in impaired T-cell responses

Cell Immunol. 2002 Feb;215(2):162-72. doi: 10.1016/s0008-8749(02)00007-2.

Abstract

IL-10 is a potent inhibitor of T-cell activation and has tolerizing effects on these cells. These effects are primarily mediated via modulation of antigen presenting cell function. Here, it is demonstrated that IL-10 completely inhibits LPS-induced DC maturation, resulting in altered DC-T-cell interactions and reduced T-cell responses. IL-10 inhibited LPS-induced upregulation of costimulatory molecules, MHC Class II, and the secretion of IL-12, TNF-alpha, IL-6, and IL-1beta by DCs, although it upregulated the SLAM (CD150) expression at both the mRNA and protein levels. IL-10 pre-treated DC did not respond to subsequent LPS activation and its stimulatory ability for allogeneic and antigen-specific T-cells was severely impaired. Importantly, T-cells derived from co-cultures with Ag-pulsed, IL-10-treated DC were impaired in their responses to subsequent Ag-specific restimulation. Transwell and DC-derived plasma membrane experiments indicated that the capacity of IL-10-treated DC to induce T-cell unresponsiveness results from alterations in the cell surface molecules rather than modulation of cytokine secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Separation
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Flow Cytometry
  • Genes, MHC Class II
  • Glycoproteins / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / physiology
  • Membrane Glycoproteins / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cell Surface
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Antigens, CD
  • CD83 antigen
  • Cytokines
  • Glycoproteins
  • Immunoglobulins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Cell Surface
  • SLAMF1 protein, human
  • Interleukin-10
  • Signaling Lymphocytic Activation Molecule Family Member 1