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
DOI: 10.1084/jem.20050011
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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.
Author information:
(1)Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, 82152
Martinsried, Germany.
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.
DOI: 10.1084/jem.20050011
PMCID: PMC2213265
PMID: 15939794 [Indexed for MEDLINE]