IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38703-2.html
   My bibliography  Save this article

Antigen recognition detains CD8+ T cells at the blood-brain barrier and contributes to its breakdown

Author

Listed:
  • Sidar Aydin

    (University of Bern)

  • Javier Pareja

    (University of Bern)

  • Vivianne M. Schallenberg

    (University of Bern)

  • Armelle Klopstein

    (University of Bern)

  • Thomas Gruber

    (University of Bern)

  • Nicolas Page

    (University and University Hospitals of Geneva)

  • Elisa Bouillet

    (University of Bern)

  • Nicolas Blanchard

    (University of Toulouse, CNRS, INSERM, UPS)

  • Roland Liblau

    (University of Toulouse, CNRS, INSERM, UPS)

  • Jakob Körbelin

    (University Medical Center Hamburg-Eppendorf)

  • Markus Schwaninger

    (University of Lübeck)

  • Aaron J. Johnson

    (Mayo Clinic)

  • Mirjam Schenk

    (University of Bern)

  • Urban Deutsch

    (University of Bern)

  • Doron Merkler

    (University and University Hospitals of Geneva)

  • Britta Engelhardt

    (University of Bern)

Abstract

Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8+ T cells are found in MS lesions, and antigen (Ag) presentation at the BBB has been proposed to promote CD8+ T cell entry into the CNS. Here, we show that brain endothelial cells process and cross-present Ag, leading to effector CD8+ T cell differentiation. Under physiological flow in vitro, endothelial Ag presentation prevented CD8+ T cell crawling and diapedesis resulting in brain endothelial cell apoptosis and BBB breakdown. Brain endothelial Ag presentation in vivo was limited due to Ag uptake by CNS-resident macrophages but still reduced motility of Ag-specific CD8+ T cells within CNS microvessels. MHC class I-restricted Ag presentation at the BBB during neuroinflammation thus prohibits CD8+ T cell entry into the CNS and triggers CD8+ T cell-mediated focal BBB breakdown.

Suggested Citation

  • Sidar Aydin & Javier Pareja & Vivianne M. Schallenberg & Armelle Klopstein & Thomas Gruber & Nicolas Page & Elisa Bouillet & Nicolas Blanchard & Roland Liblau & Jakob Körbelin & Markus Schwaninger & A, 2023. "Antigen recognition detains CD8+ T cells at the blood-brain barrier and contributes to its breakdown," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38703-2
    DOI: 10.1038/s41467-023-38703-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38703-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38703-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Josephine A. Mapunda & Javier Pareja & Mykhailo Vladymyrov & Elisa Bouillet & Pauline Hélie & Petr Pleskač & Sara Barcos & Johanna Andrae & Dietmar Vestweber & Donald M. McDonald & Christer Betsholtz , 2023. "VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38703-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.