Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion

J Exp Med. 2005 Jun 6;201(11):1805-14. doi: 10.1084/jem.20050011.


We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 microm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti-major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Autoantigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Communication / immunology*
  • Cell Movement / immunology*
  • Central Nervous System / immunology
  • Central Nervous System / pathology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Guinea Pigs
  • Histocompatibility Antigens Class II / immunology
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Microscopy, Fluorescence, Multiphoton
  • Microscopy, Video
  • Myelin Basic Protein / immunology*
  • Rats
  • Rats, Inbred Lew
  • Receptors, Antigen, T-Cell / immunology


  • Autoantigens
  • Histocompatibility Antigens Class II
  • Lymphocyte Function-Associated Antigen-1
  • Myelin Basic Protein
  • Receptors, Antigen, T-Cell