Human CD4+ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro

Open access
Date
2020Type
- Journal Article
Citations
Cited 37 times in
Web of Science
Cited 39 times in
Scopus
ETH Bibliography
yes
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Abstract
Background
The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood–brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP).
Objective
Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4+ T-cell subsets across the BBB versus the BCSFB.
Methods
Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4+ T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro.
Results
While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration.
Conclusions
Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000397739Publication status
publishedExternal links
Journal / series
Fluids and Barriers of the CNSVolume
Pages / Article No.
Publisher
BioMed CentralSubject
Blood–brain barrier; Blood-cerebrospinal fluid barrier; T-cell migration; Adhesion molecule; Multiple sclerosisOrganisational unit
09604 - Sallusto, Federica / Sallusto, Federica
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Show all metadata
Citations
Cited 37 times in
Web of Science
Cited 39 times in
Scopus
ETH Bibliography
yes
Altmetrics