W180 - Antigen-specific Interactions Between Endothelial Cells of the Blood-brain Barrier and Naive CD8 T Cells

Carmen Gonzalez-Fierro – Infinity; Vincent Cazaentre – Infinity; Guillaume Martin-Blondel – Infinity, CHU Toulouse; Jan Bauer – Medical University of Vienna; Chloé Bost – Infinity, CHU Toulouse; Roland Liblau – Infinity, CHU Toulouse

Abstract Text: It was shown that antigen-specific interactions between endothelial cells of the blood-brain barrier (BBB-EC) and activated CD8 T cells are key drivers of some pathologies affecting the central nervous system (CNS), including cerebral malaria or Susac syndrome.
However, little is known about antigen-specific interactions between BBB-EC and naïve CD8 T cells, in non-inflammatory conditions.
We used a mouse model, in which BBB-EC conditionally and inducibly express the influenza virus hemagglutinin (HA) protein as well as a TCR transgenic mouse line in which ~95% of CD8 T cells recognize the HA512-520:Kd complex, to assess antigen-specific interactions between BBB-EC and naïve CD8 T cells, in the absence of inflammation.
In vitro co-culture experiments showed that BBB-EC are able to directly activate HA-specific naïve CD8 T cells. After adoptive transfer of naïve HA-specific CD8 T cells in mice expressing or not HA in BBB-EC, we observed specific induction of activation and proliferation of the transferred cells in HA-expressing recipients.
This antigen-specific interaction leads to an accumulation of the HA-specific CD8 T cells in the CNS without patent clinical manifestations. The CNS-infiltrating CD8 T cells persist up to 90 days after injection and based on their expression of CD69 and CD103, appear to acquire a tissue-resident memory phenotype.
We assessed the consequence of this CNS-infiltrating CD8 population on a subsequent neuro-inflammatory challenge. Mice expressing HA on BBB-EC and injected with HA-specific CD8 T cells (but not CD8 of unrelated specificity) are surprisingly protected from EAE.
The mechanisms underlying this phenotype are currently under investigation.