Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion
2005-06-06 | journal article
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Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion
Kawakami, N.; Nägerl, U V.; Odoardi, F. ; Bonhoeffer, T.; Wekerle, H. & Flügel, A. (2005)
Journal of Experimental Medicine, 201(11) pp. 1805-1814. DOI: https://doi.org/10.1084/jem.20050011
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- Authors
- Kawakami, Naoto; Nägerl, U Valentin; Odoardi, Francesca ; Bonhoeffer, Tobias; Wekerle, Hartmut; Flügel, Alexander
- 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.
- Issue Date
- 6-June-2005
- Journal
- Journal of Experimental Medicine
- ISSN
- 0022-1007
- Language
- English