Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions.
Open accessAbstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Definitive evidence of a non-redundant role for monocyte-derived APC in activating autoreactive T cells is lacking.
“As both peripherally-derived and CNS-resident myeloid cells have been implicated in antigen presentation to autoreactive T cells, definitive evidence of a non-redundant role for monocyte-derived APC in activating autoreactive T cells is lacking.”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [18]
In the EAE mouse model of MS, autoreactive effector T cells first infiltrate the leptomeninges via the pial vasculature, are activated by antigen presenting meningeal/perivascular macrophages, and subsequently enter the CNS parenchyma, triggering lesion formation.
“In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, autoreactive effector T cells first infiltrate the leptomeninges via the pial vasculature, are activated by antigen presenting meningeal/perivascular macrophages, and subsequently enter the CNS parenchyma, triggering lesion formation”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Bartholomäus et al., 2009
Immune surveillance and the initiation of CNS immune responses is dependent on antigen-presenting cells that reside alongside important barriers such as perivascular spaces, leptomeningeal vessels, the choroid plexus, and the subarachnoid space.
“Immune surveillance and the initiation of CNS immune responses is dependent on antigen-presenting cells (APCs) that reside alongside important barriers such as perivascular spaces, leptomeningeal vessels, the choroid plexus, and the subarachnoid space (65-68).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [66]
Early CD4+ T cell extravasation was observed primarily through leptomeningeal vasculature in the Lewis rat model of EAE, as well as the choroid plexus in the MOG35-55 model and, to a lesser extent, postcapillary venules in the CNS parenchyma.
“Early CD4+ T cell extravasation was observed primarily through leptomeningeal vasculature in the Lewis rat model of EAE (66) as well as the choroid plexus in the MOG35-55 model (118) and, to a less extent, postcapillary venules in the CNS parenchyma.”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [66]
The citation lists haven’t been fetched yet
References 36 · Cited by 685
- Authors
- Bartholomäus, I., Kawakami, N., Odoardi, F., Schläger, C., Miljkovic, D., Ellwart, J. W., Klinkert, W. E. F., Flügel-Koch, C., Issekutz, T. B., Wekerle, H., & Flügel, A.
- Affiliations
- Max Planck Institute of Neurobiology (DE)
- Universitätsmedizin Göttingen (DE)
- Helmholtz Munich (DE)
- Dalhousie University (CA)
- Corresponding author
- Wekerle, Hartmut
- Flügel, Alexander
- Venue
- Nature
- Published
- 2009-10-14
- Volume
- 462
- Issue
- 7269
- Pages
- 94-98
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1993746949
- Cited by
- 685
- References
- 36
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 27 · 2023: 37 · 2022: 42 · 2021: 41 · 2020: 31 · 2019: 36 · 2018: 46 · 2017: 37 · 2016: 49 · 2015: 47 · 2014: 46 · 2013: 54 · 2012: 51
- FWCI
- 34.05
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- effector T cells, experimental autoimmune encephalomyelitis, multiple sclerosis, blood-brain barrier, transendothelial migration, myelin antigens, T cell activation, inflammatory cell infiltration, leptomeningeal vessels
- MeSH terms
- Animals, Antigen-Presenting Cells, Antigens, Cell Movement, Cells, Cultured, Central Nervous System Diseases, Encephalomyelitis, Autoimmune, Experimental, Meninges, Ovalbumin, Phagocytes, Rats, Inbred Lew, T-Lymphocytes, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
