Seminars in Immunopathology

, Volume 32, Issue 3, pp 275–287 | Cite as

Knocking at the brain’s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures

  • Naoto KawakamiEmail author
  • Alexander Flügel


Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease.


Two-photon imaging Autoimmunity CNS 



This work was supported by the Deutsche Forschungsgemeinschaft SFB571-C6, SFB-TR43-B2, the Multiple Sclerosis competence network “Understand MS,” and the Hertie Foundation. We thank Dr. Hartmut Wekerle for his helpful comments. We acknowledge the secretarial assistance of Mrs. Cathy Ludwig.

Open Access

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.


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Copyright information

© The Author(s) 2010

Authors and Affiliations

  1. 1.Department of NeuroimmunologyMax-Planck-Institute of NeurobiologyMartinsriedGermany
  2. 2.Department of Neuroimmunology, Institute for Multiple Sclerosis Research, Faculty of University Medical Center GöttingenUniversity of Göttingen and the Hertie FoundationGöttingenGermany

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