Intravenous tolerance modulates macrophage classical activation and antigen presentation in experimental autoimmune encephalomyelitis

J Neuroimmunol. 2009 Mar 31;208(1-2):54-60. doi: 10.1016/j.jneuroim.2009.01.002. Epub 2009 Feb 1.

Abstract

Macrophages act as the first line of self defense by mounting an inflammatory response to antigen and as antigen presenting cells to initiate the adaptive immune response. Inhibition of macrophage activation is one of the possible approaches to modulate inflammation. Intravenous (i.v.) tolerance has proved to be an effective method for ameliorating experimental autoimmune diseases. Whether macrophages are involved in tolerance induction is still largely undefined. In the present study we found that i.v. tolerance induction resulted in lower B7.1, B7.2 and MHC class II molecules, and reduced phagocytosis by both peritoneal macrophages and adherent splenocytes. Macrophages from tolerized mice were associated with a significantly impaired response of MOG-sensitized T cells to MOG. Macrophages from tolerized mice produced low levels of pro-inflammatory molecules IL-12, TNF-alpha, IL-1beta, RANTES and MCP-1 and high levels of IL-10 and TGF-beta. Administration of anti-TGF-beta led to a reduction of IL-10 in tolerized mice. Thus, i.v. tolerance inhibits macrophage classical activation and APC function, increases macrophage alternative activation and IL-10 and TGF-beta production. These cytokines, in turn, induce enhanced production of IL-10 in macrophages in MOG i.v. mice.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Autoantigens / administration & dosage
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Glycoproteins / administration & dosage
  • Glycoproteins / immunology
  • Immune Tolerance*
  • Injections, Intravenous
  • Macrophage Activation / immunology*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology

Substances

  • Autoantigens
  • Glycoproteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)