VIEWING INTO THE CNS INFLAMMATION

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Abstract


Experimental Autoimmune Encephalomyelitis (EAE) has been used for human autoimmune disease, Multiple Sclerosis (MS), which is characterized by inflammation in the Central Nerve System (CNS). In this review, we focus one of EAE variants, transfer EAE induced by adoptive transfer of encephalitogenic autoantigen specific T-cell clone. We describe about the model and introduce the application of this model for experimental research and therapeutic development. In addition, we introduce two-photon intravital imaging, which enable to observe and track fluorescently labeled encephalitogenic T-cells in living animal in real time. Further, by using activation sensors, which detect cellular activation during intravital imaging, we show migrating T-cells become activate upon contacting with local antigen presenting cells. The obtained results reveal that the transfer EAE model is useful to understand the mechanisms of initiating CNS inflammation.

Naoto Kawakami

Ludwig-Maximilians University; Max-Planck Institute of Neurobiology

Email: Naoto.kawakami@med.uni-muenchen.de
Institute of Clinical Neuroimmunology

Hartmut Wekerle

Max-Planck Institute of Neurobiology

  1. Lassmann H. Multiple sclerosis pathology: Evolution of pathogenetic concepts. Brain Pathology 2005.- Vol. 15.- Р. 217-222.
  2. Gold R., Linington C., and Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research // Brain.- 2006.- Vol. 129.- Р. 1953-1971.
  3. Ben-Nun A., Wekerle H., and Cohen I. R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis // European Journal of Immunology.- 1981.- Vol. 11.- Р. 195-199.
  4. Flügel A., Willem M., Berkowicz T., and Wekerle H. Gene transfer into CD4 + T-lymphocytes: Green fluorescent protein engineered, encephalitogenic T cells used to illuminate immune responses in the brain // Nature Medicine.- 1999.- Vol. 5.- Р. 843-847.
  5. Flügel A., Berkowicz T., Ritter T. et al. Migratory activity and functional changes of green fluorescent effector T-cells before and during experimental autoimmune encephalomyelitis // Immunity.- 2001.- Vol. 14.- Р. 547-560.
  6. Mathey E. K., Derfuss T., Storch M. K. et al. Neurofascin as a novel target for autoantibody-mediated axonal injury // Journal of Experimental Medicine.- 2007.- Vol. 204.- Р. 2363-2372.
  7. Bradl M., Misu T., Takahashi T. et al. Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo // Annals of Neurology.- 2009.- Vol. 66.- Р. 630-643.
  8. Bartholomäus I., Kawakami N., Odoardi F. et al. Effector T-cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions // Nature.- 2009.- Vol. 462.- Р. 94-98.
  9. Odoardi F., Kawakami N., Li Z. X. et al. Instant effect of soluble antigen on effector T-cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis // Proceedings of the National Academy of Sciences (USA).- 2007.- Vol. 104.- Р. 920-925.
  10. Odoardi F., Kawakami N., Klinkert W. E. F. et al. Blood-borne soluble protein antigen intensifies T-cell activation in autoimmune CNS lesions and exacerbates clinical disease // Proceedings of the National Academy of Sciences (USA).- 2007.- Vol. 104.- Р. 18625-18630.
  11. Kawakami N., Lassmann S., Li Z. et al. The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis // Journal of Experimental Medicine.- 2004.- Vol. 199.- Р. 185-197.
  12. Cordiglieri C., Odoardi F., Zhang B. et al. Nicotinic acid adenine dinucleotide phosphate-mediated calcium signalling in effector T-cells regulates autoimmunity of the central nervous system. Brain.- 2010.- Vol. 133.- Р. 1930-1943.
  13. Kawakami N., and Flügel A. Knocking at the brain’s door: intravital two-photon imaging of autoreactive T-cell interactions with CNS structures // Semin. Immunopathol.- 2010.- Vol. 32.- Р. 275-287.
  14. Kawakami N., Bartholomaus I., Pesic M., and Mues M. An autoimmunity odyssey: how autoreactive T-cells infiltrate into the CNS // Immunol Rev.- 2012.- Vol. 248.- Р. 140-155.
  15. Helmchen F. and Denk W. Deep tissue two-photon microscopy // Nature Methods.- 2005.- Vol. 2.- Р. 932-940.
  16. Ransohoff R. M. Natalizumab for multiple sclerosis // New England Journal of Medicine.- 2007.- Vol. 356.- Р. 2622-2629.
  17. Greter M., Heppner F. L., Lemos M. P. et al. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis // Nature Medicine.- 2005.- Vol. 11.- Р. 328-334.
  18. Kawakami N., Nägerl U. V., Odoardi F. et al. Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion // Journal of Experimental Medicine.- 2005.- Vol. 201.- Р. 1805-1814.
  19. Ohhora M., and Rao A. Calcium signaling in lymphocytes // Current Opinion in Immunology.- 2008.- Vol. 20.- Р. 250-258.
  20. Mank M., Santos A. F., Direnberger S. et al. A genetically encoded calcium indicator for chronic in vivo two-photon imaging // Nature Methods.- 2008.- Vol. 5.- Р. 805-811.
  21. Mues M., Bartholomaus I., Thestrup T. et al. Real-time in vivo analysis of T-cell activation in the central nervous system using a genetically encoded calcium indicator // Nature Medicine.- 2013.- Vol. 19.- Р. 778-783.
  22. Pesic M., Bartholomaus I., Kyratsous N. I. et al. 2-photon imaging of phagocyte-mediated T-cell activation in the CNS // J. Clin. Invest.- 2013.- Vol. 123.- Р. 1192-1201.
  23. Lodygin D., Odoardi F., Schlager C. et al. A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T-cell activation in real time during CNS autoimmunity // Nat Med.- 2013.- Vol. 19.- Р. 784-790.

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