Contributions
Abstract: P456
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Background: A body of evidence highlights the involvement of CD8+T cells in Multiple sclerosis (MS). We have recently demonstrated that overrepresented (oligoclonal) CD8+T cells found at lesion sites, thought to be driven by local cognate antigens, are the same overrepresented T cells found in the CSF of the same patients and represent up to 47% of the overrepresented blood CD8+ T cells. Based on these previous results, the CSF and the blood can be used as a source of T cells involved in the disease process. However, to date we have not identified yet, in the periphery, the culprit CD8+T cells driving autoimmune inflammation nor their phenotype and/or function. Our working hypothesis is that the cells able to provoke damages in the CNS may have a specific phenotypic or functional pattern.
Methods: To analyze single-cells molecular signatures, we isolate single memory CD8+T cells from the blood and CSF from MS patients, Healthy Controls (HC) and patients with other neurological diseases (OND) and performed amplifications of 96 well-chosen genes together with their TCR Vβ chain.In parallel, we performed a TRBV deep immunosequencing on a pool of memory CD8+T cells to identify the expanded clones in the samples.
Results: We observed a clear clustering of MS single-cells highly different from HC and OND with numerous genes involved in T cell activation, effector function, cytotoxicity, and cell migration. Moreover, when analyzing the molecular profile of oligoclonally expanded CD8+ T cells, we observed that they harbor a specific pattern with an increased expression of activation genes. Finally, we also found only in MS patients and not in OND that the CSF CD8+ T cells and those from the blood have a similar profile with expression of migration markers allowing blood CD8+T cells to migrate to the central nervous system (CNS).
Interpretation: Our data are the first to describe a specific molecular pattern of memory CD8+T cells from blood and CSF in MS patients and to link this pattern to the cell clonality. We detect a specific signature of MS single cells orienting the cells toward an activated, effector and cytotoxic profile and allowing the cells to migrate to the CNS.
Disclosure:
Dugast Emilie: Nothing to disclose
Vogel Isabel: Nothing to disclose
Garcia Alexandra: Nothing to disclose
Nicol Bryan: Nothing to disclose
Morille Jérémy: Nothing to disclose
Jacq-Foucher Marylène: Nothing to disclose
Jousset Natacha: Nothing to disclose
Le Frère Fabienne: Nothing to disclose
Wiertlewski Sandrine: Nothing to disclose
Tarte Karin: Nothing to disclose
Nicot Arnaud: Nothing to disclose
Michel Laure: Nothing to disclose
Berthelot Laureline: Nothing to disclose
Gourraud Pierre-Antoine: Nothing to disclose
Laplaud David-Axel: Nothing to disclose
Abstract: P456
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Background: A body of evidence highlights the involvement of CD8+T cells in Multiple sclerosis (MS). We have recently demonstrated that overrepresented (oligoclonal) CD8+T cells found at lesion sites, thought to be driven by local cognate antigens, are the same overrepresented T cells found in the CSF of the same patients and represent up to 47% of the overrepresented blood CD8+ T cells. Based on these previous results, the CSF and the blood can be used as a source of T cells involved in the disease process. However, to date we have not identified yet, in the periphery, the culprit CD8+T cells driving autoimmune inflammation nor their phenotype and/or function. Our working hypothesis is that the cells able to provoke damages in the CNS may have a specific phenotypic or functional pattern.
Methods: To analyze single-cells molecular signatures, we isolate single memory CD8+T cells from the blood and CSF from MS patients, Healthy Controls (HC) and patients with other neurological diseases (OND) and performed amplifications of 96 well-chosen genes together with their TCR Vβ chain.In parallel, we performed a TRBV deep immunosequencing on a pool of memory CD8+T cells to identify the expanded clones in the samples.
Results: We observed a clear clustering of MS single-cells highly different from HC and OND with numerous genes involved in T cell activation, effector function, cytotoxicity, and cell migration. Moreover, when analyzing the molecular profile of oligoclonally expanded CD8+ T cells, we observed that they harbor a specific pattern with an increased expression of activation genes. Finally, we also found only in MS patients and not in OND that the CSF CD8+ T cells and those from the blood have a similar profile with expression of migration markers allowing blood CD8+T cells to migrate to the central nervous system (CNS).
Interpretation: Our data are the first to describe a specific molecular pattern of memory CD8+T cells from blood and CSF in MS patients and to link this pattern to the cell clonality. We detect a specific signature of MS single cells orienting the cells toward an activated, effector and cytotoxic profile and allowing the cells to migrate to the CNS.
Disclosure:
Dugast Emilie: Nothing to disclose
Vogel Isabel: Nothing to disclose
Garcia Alexandra: Nothing to disclose
Nicol Bryan: Nothing to disclose
Morille Jérémy: Nothing to disclose
Jacq-Foucher Marylène: Nothing to disclose
Jousset Natacha: Nothing to disclose
Le Frère Fabienne: Nothing to disclose
Wiertlewski Sandrine: Nothing to disclose
Tarte Karin: Nothing to disclose
Nicot Arnaud: Nothing to disclose
Michel Laure: Nothing to disclose
Berthelot Laureline: Nothing to disclose
Gourraud Pierre-Antoine: Nothing to disclose
Laplaud David-Axel: Nothing to disclose