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

Hideaki Nishihara (1) , Sasha Soldati (1) , Adrien Mossu (2, 1) , Maria Rosito (3, 1) , Henriette Rudolph (4) , William Muller (5) , Daniela Latorre (6) , Federica Sallusto (7, 6) , Mireia Sospedra (8) , Roland Martin (8) , Hiroshi Ishikawa (9) , Tobias Tenenbaum (10) , Horst Schroten (10) , Fabien Gosselet (11) , Britta Engelhardt (1)

1 Theodor Kocher Institute
2 R&D TranscureBioservices
3 CLNS - Center for Life NanoScience [Rome, Italie]
4 University Hospital Mannheim | Universitätsmedizin Mannheim
5 Feinberg School of Medicine
6 USI - Università della Svizzera italiana = University of Italian Switzerland
7 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
8 UZH - Universität Zürich [Zürich] = University of Zurich
9 Université de Tsukuba = University of Tsukuba
10 Universität Heidelberg [Heidelberg] = Heidelberg University
11 LBHE - Laboratoire de la Barrière Hémato-Encéphalique

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.

Mots clés: T-cell migration; Adhesion molecule; Blood-cerebrospinal fluid barrier; Blood–brain barrier; Multiple sclerosis

Domaines: Neurobiologie; Organisation et fonctions cellulaires [q-bio.SC]; Immunité adaptative

Hideaki Nishihara, Sasha Soldati, Adrien Mossu, Maria Rosito, Henriette Rudolph, et al.. Human CD4+ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro. Fluids and Barriers of the CNS, 2020, 17, pp.3. ⟨10.1186/s12987-019-0165-2⟩. ⟨hal-02505269⟩