1. Max Planck Institute for Neurobiology, 82152 Martinsried, Germany
2. Department of Neuroimmunology, Institute for Multiple Sclerosis Research, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, 37073 Göttingen, Germany
3. Institute for Immunology, Ludwig-Maximilians-University, 80336 Munich, Germany
4. Institute for Experimental Hematology, Helmholtz Centre, 81377 Munich, Germany
5. Institute for Anatomy 2, Friedrich-Alexander-University, 91054 Erlangen, Germany
6. Division of Immunology, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada
7. These authors contributed equally to this work.

Correspondence to: Hartmut Wekerle¹Alexander Flügel^1,2,3 Correspondence and requests for materials should be addressed to A.F. (Email: Fluegel@med.uni-goettingen.de) or H.W. (Email: hwekerle@neuro.mpg.de).

Abstract

The tissues of the central nervous system are effectively shielded from the blood circulation by specialized vessels that are impermeable not only to cells, but also to most macromolecules circulating in the blood. Despite this seemingly absolute seclusion, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attacks¹. Using intravital two-photon imaging in a Lewis rat model of experimental autoimmune encephalomyelitis, here we present in real-time the interactive processes between effector T cells and cerebral structures from their first arrival to manifest autoimmune disease. We observed that incoming effector T cells successively scanned three planes. The T cells got arrested to leptomeningeal vessels and immediately monitored the luminal surface, crawling preferentially against the blood flow. After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal (pial) membrane. There, the T cells encountered phagocytes that effectively present antigens, foreign as well as myelin proteins. These contacts stimulated the effector T cells to produce pro-inflammatory mediators, and provided a trigger to tissue invasion and the formation of inflammatory infiltrations.

1. Max Planck Institute for Neurobiology, 82152 Martinsried, Germany
2. Department of Neuroimmunology, Institute for Multiple Sclerosis Research, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, 37073 Göttingen, Germany
3. Institute for Immunology, Ludwig-Maximilians-University, 80336 Munich, Germany
4. Institute for Experimental Hematology, Helmholtz Centre, 81377 Munich, Germany
5. Institute for Anatomy 2, Friedrich-Alexander-University, 91054 Erlangen, Germany
6. Division of Immunology, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada
7. These authors contributed equally to this work.

Correspondence to: Hartmut Wekerle¹Alexander Flügel^1,2,3 Correspondence and requests for materials should be addressed to A.F. (Email: Fluegel@med.uni-goettingen.de) or H.W. (Email: hwekerle@neuro.mpg.de).

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