Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions

By Ingo Bartholomäus, N. Kawakami, F. Odoardi, Christian Schläger, D. Miljkovic, J. Ellwart, W. Klinkert, C. Flügel-Koch, T. Issekutz, H. Wekerle and 1 more. Nature, 2009

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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 attacks. 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.

Subfields: Immunology, Immunology and Allergy, Neurology

View Paper: https://www.semanticscholar.org/paper/3266c99de73a70077b550bc0b0a57fbf1805a3ef

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Citations in the corpus

The blood–brain barrier in systemic infection and inflammation (2021, background): “After traversing the endothelial layer of the basement membrane, leukocytes tend to be held up in the perivascular space [52] and may survey the perivascular space at length [53].”
Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation (2019, background): “Because T cells arrest in response to antigen recognition (19), these observations support an important role for infiltrating myeloid cells in the activation of T cells during EAE.”
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis (2010, background): “These cells could then recirculate and could be restimulated at leptomeningeal vessels by antigen-presenting phagocytes, to invade CNS tissue”
Leukocyte migration into inflamed tissues. (2014, background): “, 2011) and extravasating CD4 T cells can readily interact with antigenic moieties presented by perivascular macrophages at various chronic sites of inflammation (Bartholomäus et al., 2009).”
Extracellular matrix: a dynamic niche component during cancer progression (2012, positive): “Studies using EM and, more recently, intravital imaging have shown that transmi gration across the endothelial basement membrane is a rate limiting step during T cell extravasation (Wang et al., 2006; Bartholomäus et al., 2009).”
BRAIN REGENERATION IN PHYSIOLOGY AND PATHOLOGY: THE IMMUNE SIGNATURE DRIVING THERAPEUTIC PLASTICITY OF NEURAL STEM CELLS (2011, background): “There is now evidence that antigens from the CNS are processed locally by professional antigen presenting cells, such as dendritic cells (DCs), which migrate from the CSF to cervical lymph nodes (99).”
The blood–brain barrier in health and disease: Important unanswered questions (2020, background): “It will be necessary to ensure that targeting these molecules does not produce secondary effects; Alcam knockout mice develop more severe EAE as ALCAM also enforces TJ integrity (Lécuyer et al., 2017).”
Recruitment of Beneficial M2 Macrophages to Injured Spinal Cord Is Orchestrated by Remote Brain Choroid Plexus (2013, neutral): “The leptomeninges and the CP, recently identified as CNS entry sites for leukocytes (Bartholomäus et al., 2009; Reboldi et al., 2009), were therefore examined.”