Contributions
Abstract: 114
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
CD8 T cells are key players of the adaptive immune response involved in the pathogenesis of inflammatory and infectious diseases multiple sclerosis. Mechanisms of penetration of CD8 T cells in CNS are not completely elucidated. A role for antigen expression by MHC-I molecules expressed by endothelial cells (EC) of the blood brain barrier (BBB) has been suggested. The aim of this project is to unravel the role of antigen presentation specifically by EC of the BBB on the activation, migration and pathogenicity of CD8 T cells in the central nervous system (CNS). We generated a murine model in which HA (Haemagglutinin of the Influenza virus) is conditionally expressed after tamoxifen administration only by EC of the BBB and epithelial cells of choroid plexus. CD8 T cells bearing HA-specific TCR were in vitro differentiated toward a cytotoxic phenotype and transferred into tamoxifen-treated Slco1c1ERT2-HA mice (HA+) or control mice (HA-). The adoptive transfer of 3*107 HA-specific cytotoxic CD8 T cells in HA+ mice is associated with a significant weight loss at day 8, but not in HA- mice. Brain immunochemistry performed 8 and 28 days after adoptive transfer showed that CD3+ cells penetrate the CNS parenchyma only in HA+ mice and lead to CNS barriers damages and alteration of BBB permeability. FACS analysis of the composition of CNS T cell infiltrates 7 days after cell transfer using a congenic marker revealed a significant increase in the number of transferred CD8 T cells in HA+ mice compared to HA-. We developed co-culture experiments in which HA-expressing EC (or control EC) will be seeded with naïve HA-specific CD8 T cells. After FACS analysis of CD8 T cells, EC appear to elicit activation of HA-specific CD8 T cells in an antigen-dependent manner. Our results showed us that the specific expression of a self antigen by the EC of the BBB allows antigen-specific cytotoxic CD8 T cells to migrate into the CNS. Our results showed us that, in this original murine model, the specific expression of a neo-self antigen by the endothelial cells of the BBB allows activation of antigen-specific naïve CD8 T cells both in vitro and in vivo and induce their proliferation in vivo. In case of cytotoxic antigen-specific cytotoxic CD8 T cells, EC induce their migration inside the CNS. These observations highlight that endothelial cells acting as semi-professional antigen presenting cells could be involved in infectious or inflammatory CNS diseases.
Disclosure: Céline Meyer: nothing to disclose
Chloé Laplagne : nothing to disclose
Lidia Yshii : nothing to disclose
Émille Mauré : nothing to disclose
Christina Gebauer : nothing to disclose
Britta Engelhardt : nothing to disclose
Jan Bauer : nothing to disclose
Roland Liblau : nothing to disclose
Guillaume Martin-Blondel : nothing to disclose
Abstract: 114
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
CD8 T cells are key players of the adaptive immune response involved in the pathogenesis of inflammatory and infectious diseases multiple sclerosis. Mechanisms of penetration of CD8 T cells in CNS are not completely elucidated. A role for antigen expression by MHC-I molecules expressed by endothelial cells (EC) of the blood brain barrier (BBB) has been suggested. The aim of this project is to unravel the role of antigen presentation specifically by EC of the BBB on the activation, migration and pathogenicity of CD8 T cells in the central nervous system (CNS). We generated a murine model in which HA (Haemagglutinin of the Influenza virus) is conditionally expressed after tamoxifen administration only by EC of the BBB and epithelial cells of choroid plexus. CD8 T cells bearing HA-specific TCR were in vitro differentiated toward a cytotoxic phenotype and transferred into tamoxifen-treated Slco1c1ERT2-HA mice (HA+) or control mice (HA-). The adoptive transfer of 3*107 HA-specific cytotoxic CD8 T cells in HA+ mice is associated with a significant weight loss at day 8, but not in HA- mice. Brain immunochemistry performed 8 and 28 days after adoptive transfer showed that CD3+ cells penetrate the CNS parenchyma only in HA+ mice and lead to CNS barriers damages and alteration of BBB permeability. FACS analysis of the composition of CNS T cell infiltrates 7 days after cell transfer using a congenic marker revealed a significant increase in the number of transferred CD8 T cells in HA+ mice compared to HA-. We developed co-culture experiments in which HA-expressing EC (or control EC) will be seeded with naïve HA-specific CD8 T cells. After FACS analysis of CD8 T cells, EC appear to elicit activation of HA-specific CD8 T cells in an antigen-dependent manner. Our results showed us that the specific expression of a self antigen by the EC of the BBB allows antigen-specific cytotoxic CD8 T cells to migrate into the CNS. Our results showed us that, in this original murine model, the specific expression of a neo-self antigen by the endothelial cells of the BBB allows activation of antigen-specific naïve CD8 T cells both in vitro and in vivo and induce their proliferation in vivo. In case of cytotoxic antigen-specific cytotoxic CD8 T cells, EC induce their migration inside the CNS. These observations highlight that endothelial cells acting as semi-professional antigen presenting cells could be involved in infectious or inflammatory CNS diseases.
Disclosure: Céline Meyer: nothing to disclose
Chloé Laplagne : nothing to disclose
Lidia Yshii : nothing to disclose
Émille Mauré : nothing to disclose
Christina Gebauer : nothing to disclose
Britta Engelhardt : nothing to disclose
Jan Bauer : nothing to disclose
Roland Liblau : nothing to disclose
Guillaume Martin-Blondel : nothing to disclose