Contributions
Abstract: EP1429
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Whereas the cause of multiple sclerosis (MS) is multifactorial, a central role has been attributed to autoimmune responses against components of the myelin sheath coating nerve cells of the CNS. The myelin sheath is a rich source of sulfatides and galactosylceramides. Recent studies have identified sulfatide-reactive TCR γδ T cells among human peripheral blood lymphocytes (PBL). These γδ T cells were CD1d- or CD1c-restricted, and preferentially used the TCR Vδ1-segment, a TCR previously identified in MS lesions.
Objective: We have investigated Vδ1 T cells in PBL and cerebrospinal fluid (CSF) of newly-diagnosed MS patients using 14-color flow cytometry.
Results: Vδ1 cells showed signs of recent activation in MS CSF and its frequency among total γδ T cells was significantly increased in patients compared with healthy donors (HD). Strikingly, newly-diagnosed MS patients had an increased frequency of IFN-γ-producing Vδ1 cells in PBL compared with HD, while there was no change in other T cell subsets analyzed. This contrasts to the anti-inflammatory profile normally associated with Vδ1 cells. The frequency of IFN-γ-producing Vδ1 cells positively correlated with markers for neuronal damage and disease activity. MS patients treated with natalizumab (blocking integrin a-4 and thereby leukocyte homing to the CNS) had normalized level of IFN-g-producing Vδ1 cells.
Conclusion: Taken together, this suggests that Vδ1 cells are recently activated in newly-diagnosed MS patients and may contribute to the early MS pathogenesis by producing proinflammatory cytokines.
Disclosure: Lenka Novakova, Avadhesh Kumar Singh, Henrik Zetterberg, and Susanna Cardell have no discloures. Clas Malmeström has received honoraria for lectures and advisory boards from and Novartis Markus Axelsson have had compensation for lectures and/or advisory boards from Biogen, Genzyme and Novartis. Jan Lycke has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva.
Abstract: EP1429
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Whereas the cause of multiple sclerosis (MS) is multifactorial, a central role has been attributed to autoimmune responses against components of the myelin sheath coating nerve cells of the CNS. The myelin sheath is a rich source of sulfatides and galactosylceramides. Recent studies have identified sulfatide-reactive TCR γδ T cells among human peripheral blood lymphocytes (PBL). These γδ T cells were CD1d- or CD1c-restricted, and preferentially used the TCR Vδ1-segment, a TCR previously identified in MS lesions.
Objective: We have investigated Vδ1 T cells in PBL and cerebrospinal fluid (CSF) of newly-diagnosed MS patients using 14-color flow cytometry.
Results: Vδ1 cells showed signs of recent activation in MS CSF and its frequency among total γδ T cells was significantly increased in patients compared with healthy donors (HD). Strikingly, newly-diagnosed MS patients had an increased frequency of IFN-γ-producing Vδ1 cells in PBL compared with HD, while there was no change in other T cell subsets analyzed. This contrasts to the anti-inflammatory profile normally associated with Vδ1 cells. The frequency of IFN-γ-producing Vδ1 cells positively correlated with markers for neuronal damage and disease activity. MS patients treated with natalizumab (blocking integrin a-4 and thereby leukocyte homing to the CNS) had normalized level of IFN-g-producing Vδ1 cells.
Conclusion: Taken together, this suggests that Vδ1 cells are recently activated in newly-diagnosed MS patients and may contribute to the early MS pathogenesis by producing proinflammatory cytokines.
Disclosure: Lenka Novakova, Avadhesh Kumar Singh, Henrik Zetterberg, and Susanna Cardell have no discloures. Clas Malmeström has received honoraria for lectures and advisory boards from and Novartis Markus Axelsson have had compensation for lectures and/or advisory boards from Biogen, Genzyme and Novartis. Jan Lycke has received travel support and/or lecture honoraria from Biogen, Novartis, Teva and Genzyme/SanofiAventis; has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme/SanofiAventis; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, Novartis and Teva.