Journal of Neuroimmune Pharmacology

, Volume 12, Issue 2, pp 305–313 | Cite as

Phenotype of Antigen Unexperienced TH Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis

  • Sophia Franck
  • Magdalena Paterka
  • Jerome Birkenstock
  • Frauke Zipp
  • Volker Siffrin
  • Esther Witsch


Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.


Intravital two-photon microscopy Multiple sclerosis Experimental autoimmune encephalomyelitis Migration Naive TH cell 



Antigen presenting cells


Blood-brain barrier


CC-chemokine ligand 21


Central nervous system


Experimental autoimmune encephalomyelitis


Intercellular adhesion molecule 1








Leukocyte function-associated antigen 1


Magnetic cell sorting


Myelin oligodendroycte glycoprotein35-55


Multiple sclerosis




Proteolipid protein

Rag 1-/-

B6.129S7-Rag1tm1Mom/J mice

TH cell

T helper cell


Two-photon laser scanning microscopy


Vascular cell adhesion molecule


Very late antigen-4



This study has been supported by the German Research Foundation (DFG, SFB-TR 128/B9 to VS and FZ).

Compliance with Ethical Standards


We thank Heike Ehrengard and Christin Liefländer for technical assistance and Cheryl Ernest for proofreading the manuscript.

SF was responsible for executing the research project and writing the manuscript, performing all experiments, preparing the figures and the statistical analysis. EW assisted in data analysis and writing and editing the manuscript. JB assisted technically with research. MP assisted with data analysis. VS contributed to the design of the experiments and assisted with data analysis. FZ assisted in editing the manuscript. VS and FZ directed all aspects of this research project including the experimental design.

Conflict of Interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sophia Franck
    • 1
  • Magdalena Paterka
    • 1
  • Jerome Birkenstock
    • 1
  • Frauke Zipp
    • 1
  • Volker Siffrin
    • 1
  • Esther Witsch
    • 1
  1. 1.Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2)University Medical Center of the Johannes Gutenberg UniversityMainzGermany

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