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

Abstract

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.

• Authors: Naoto Kawakami, U Valentin Nägerl, Francesca Odoardi, Tobias Bonhoeffer, Hartmut Wekerle, Alexander Flügel
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 201 Issue 11 Pg. 1805-14 (Jun 06 2005) ISSN: 0022-1007 [Print] United States
• PMID: 15939794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Antigen Presentation (immunology)
• Autoantigens (immunology)
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Cell Communication (immunology)
• Cell Movement (immunology)
• Central Nervous System (immunology, pathology)
• Encephalomyelitis, Autoimmune, Experimental (immunology, 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)