A paradoxical role of APCs in the induction of intravenous tolerance in experimental autoimmune encephalomyelitis

J Neuroimmunol. 2005 Apr;161(1-2):101-12. doi: 10.1016/j.jneuroim.2004.12.017.

Abstract

The central role of T cells in the induction of tolerance to autoantigens has been well documented. However, the role of antigen-presenting cells (APCs) in this process is not yet fully understood. To better understand the contribution of APCs in tolerance, we studied the interaction of purified APCs and CD4(+) T cells in a model of intravenous (i.v.) tolerance to experimental autoimmune encephalomyelitis (EAE). As expected, we found that T cells were tolerized to the autoantigen after i.v. injection. However, purified APCs obtained from MOG-i.v.-treated mice were paradoxically immuno-stimulatory, as they induced a non-specific Th1-type response both in vitro and in vivo. We conclude that blocking such APC activation would enhance the effectiveness of tolerance induction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / physiology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Proliferation / drug effects
  • Coculture Techniques / methods
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Flow Cytometry / methods
  • Glycoproteins
  • Immune Tolerance / physiology*
  • Immunization, Passive
  • Injections, Intravenous / methods
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • RNA, Messenger / biosynthesis
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Cytokines
  • Glycoproteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Cytokine
  • myelin oligodendrocyte glycoprotein (35-55)