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2-photon imaging of phagocyte-mediated T cell activation in the CNS

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons61113

Pesic,  Marija
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons38757

Bartholomäus,  Ingo
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons39114

Wekerle,  Hartmut
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons38918

Kawakami,  Naoto
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Zitation

Pesic, M., Bartholomäus, I., Kyratsous, N. I., Heissmeyer, V., Wekerle, H., & Kawakami, N. (2013). 2-photon imaging of phagocyte-mediated T cell activation in the CNS. JOURNAL OF CLINICAL INVESTIGATION, 123(3), 1192-1201. doi:10.1172/JCI67233.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-000E-FADA-8
Zusammenfassung
Autoreactive T cells can infiltrate the CNS to cause disorders such as multiple sclerosis. In order to visualize T cell activation in the CNS, we introduced a truncated fluorescent derivative of nuclear factor of activated T cells (NFAT) as a real-time T cell activation indicator. In experimental autoimmune encephalomyelitis, a rat model of multiple sclerosis, we tracked T cells interacting with structures of the vascular blood-brain barrier (BBB). 2-photon imaging documented the cytoplasmic-nuclear translocation of fluorescent NFAT, indicative of calcium-dependent activation of the T cells in the perivascular space, but not within the vascular lumen. The activation was related to contacts with the local antigen-presenting phagocytes and was noted only in T cells with a high pathogenic potential. T cell activation implied the presentation of an autoantigen, as the weakly pathogenic T cells, which remained silent in the untreated hosts, were activated upon instillation of exogenous autoantigen. Activation did not cogently signal long-lasting arrest, as individual T cells were able to sequentially contact fresh APCs. We propose that the presentation of local autoantigen by BBB-associated APCs provides stimuli that guide autoimmune T cells to the CNS destination, enabling them to attack the target tissue.