Contributions
Abstract: P981
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Objective: CD8 T cells are the most numerous infiltrating T cells in central nervous system (CNS) lesions of multiple sclerosis (MS) and several lines of evidence support their role in tissue damage. However, to date the precise phenotype of the circulating CD8 T cells that may be recruited from the periphery to invade the CNS remains largely undefined. It has been suggested that Tc17 lymphocytes may be involved and in humans, these cells are characterized by the expression of CD161. Whereas CD8+ T cells with a high CD161 expression, representing mainly Mucosal Associated Invariant T cells, are likely not involved in the disease process, CD8+ T cells with CD161 intermediate expression constitute a unique, recently described subset of CD8+ T cells. Yet, its role in neuro-inflammation has not been investigated.
Methods: Frequency, phenotype and function of CD8 T cells with an intermediate expression of CD161 were characterized ex-vivo, in vitro and in situ using RNAseq, RT-PCR, flow cytometry, TCR sequencing and immunofluorescence from healthy volunteers, MS subjects and inflammatory and non-inflammatory controls.
Results: We report here that CD8+CD161int T cells present several characteristics of effector cells with abilities to cross the blood-brain-barrier and to secrete IL-17, IFNg, GM-CSF and IL-22. We further demonstrate that these cells are recruited and enriched in the CNS of MS subjects where they produce IL-17. In the periphery, RNAseq, RT-PCR, high Throughput TCR repertoire analyses and flow cytometry confirmed an increased effector and transmigration pattern of these cells in MS patients with the presence of supernumerary clones compared to healthy controls.
Interpretation: Our data demonstrate that CD161 with intermediate expression identifies activated and effector CD8+ T cells with pathogenic properties recruited in MS lesions. They suggest that CD161 may represent a suitable biomarker and a valid target for the treatment of neuroinflammation.
Disclosure:
DAL received honoraria or unconditional grants from Biogen, Novartis, Sanofi-Genzyme, Teva, Merck, Roche and Medday.
SW received honoraria from Biogen, Novartis, Sanofi-Genzyme, Roche and Merck.
All other authors have nothing to disclose.
Abstract: P981
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Objective: CD8 T cells are the most numerous infiltrating T cells in central nervous system (CNS) lesions of multiple sclerosis (MS) and several lines of evidence support their role in tissue damage. However, to date the precise phenotype of the circulating CD8 T cells that may be recruited from the periphery to invade the CNS remains largely undefined. It has been suggested that Tc17 lymphocytes may be involved and in humans, these cells are characterized by the expression of CD161. Whereas CD8+ T cells with a high CD161 expression, representing mainly Mucosal Associated Invariant T cells, are likely not involved in the disease process, CD8+ T cells with CD161 intermediate expression constitute a unique, recently described subset of CD8+ T cells. Yet, its role in neuro-inflammation has not been investigated.
Methods: Frequency, phenotype and function of CD8 T cells with an intermediate expression of CD161 were characterized ex-vivo, in vitro and in situ using RNAseq, RT-PCR, flow cytometry, TCR sequencing and immunofluorescence from healthy volunteers, MS subjects and inflammatory and non-inflammatory controls.
Results: We report here that CD8+CD161int T cells present several characteristics of effector cells with abilities to cross the blood-brain-barrier and to secrete IL-17, IFNg, GM-CSF and IL-22. We further demonstrate that these cells are recruited and enriched in the CNS of MS subjects where they produce IL-17. In the periphery, RNAseq, RT-PCR, high Throughput TCR repertoire analyses and flow cytometry confirmed an increased effector and transmigration pattern of these cells in MS patients with the presence of supernumerary clones compared to healthy controls.
Interpretation: Our data demonstrate that CD161 with intermediate expression identifies activated and effector CD8+ T cells with pathogenic properties recruited in MS lesions. They suggest that CD161 may represent a suitable biomarker and a valid target for the treatment of neuroinflammation.
Disclosure:
DAL received honoraria or unconditional grants from Biogen, Novartis, Sanofi-Genzyme, Teva, Merck, Roche and Medday.
SW received honoraria from Biogen, Novartis, Sanofi-Genzyme, Roche and Merck.
All other authors have nothing to disclose.