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Journal Article

T cells become licensed in the lung to enter the central nervous system

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons39090

Streyl,  Kristina
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons39102

Ulaganathan,  Vijay Kumar
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons71875

Heckelsmiller,  Klaus
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50445

Nietfeld,  Wilfried
Dept. of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons38928

Klinkert,  Wolfgang E. F.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50564

Spang,  Rainer
Dept. of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50409

Lehrach,  Hans
Dept. of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50613

Vingron,  Martin
Dept. of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Max Planck Society;

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

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

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Citation

Odoardi, F., Sie, C., Streyl, K., Ulaganathan, V. K., Schlaeger, C., Lodygin, D., et al. (2012). T cells become licensed in the lung to enter the central nervous system. NATURE, 488(7413), 675-679. doi:10.1038/nature11337.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000F-EEC8-9
Abstract
The blood-brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB1,2 and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma(3-6). Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. Instead, intravenously transferred T-cell blasts gain the capacity to enter the CNS after residing transiently within the lung tissues. Inside the lung tissues, they move along and within the airways to bronchus-associated lymphoid tissues and lung-draining mediastinal lymph nodes before they enter the blood circulation from where they reach the CNS. Effector T cells transferred directly into the airways showed a similar migratory pattern and retained their full pathogenicity. On their way the T cells fundamentally reprogrammed their gene-expression profile, characterized by downregulation of their activation program and upregulation of cellular locomotion molecules together with chemokine and adhesion receptors. The adhesion receptors include ninjurin 1, which participates in T-cell intravascular crawling on cerebral blood vessels. We detected that the lung constitutes a niche not only for activated T cells but also for resting myelin-reactive memory T cells. After local stimulation in the lung, these cells strongly proliferate and, after assuming migratory properties, enter the CNS and induce paralytic disease. The lung could therefore contribute to the activation of potentially autoaggressive T cells and their transition to a migratory mode as a prerequisite to entering their target tissues and inducing autoimmune disease.