Phenotype of Antigen Unexperienced THCells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis.
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.
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.
Sophia
S
Franck
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.
Magdalena
M
Paterka
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.
Jerome
J
Birkenstock
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.
Frauke
F
Zipp
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.
Volker
V
Siffrin
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany. esther.witsch@gmail.com.
Esther
E
Witsch
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*
D000941:Antigens
Experimental autoimmune encephalomyelitis; Intravital two-photon microscopy; Migration; Multiple sclerosis; Naive TH cell