Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion.
J Exp Med. 2005-06-06; 201(11): 1805-1814
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1. J Exp Med. 2005 Jun 6;201(11):1805-14.
Live imaging of effector cell trafficking and autoantigen recognition within the
unfolding autoimmune encephalomyelitis lesion.
Kawakami N(1), Nägerl UV, Odoardi F, Bonhoeffer T, Wekerle H, Flügel A.
(1)Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, 82152
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
PMID: 15939794 [Indexed for MEDLINE]