Contributions
Abstract: P736
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Pathology
Introduction: Genetic and pathology studies point to a central role of T cell-mediated inflammation in the pathophysiology of multiple sclerosis (MS). Recently, we showed the human brain to be populated by tissue resident memory T (TRM) cells.
Objectives: We explored the distribution of TRM cell markers on white matter-derived T cells of MS brain donors, and explored correlations between T cells and the presence of chronic active lesions in post-mortem brain tissue.
Methods: From brain donors of the Netherlands Brainbank with MS (n=5) and without MS (n=12), cells were isolated from normal appearing white matter acquired during rapid post-mortem autopsies, and analyzed with flowcytometry. Immunohistochemistry for HLA-PLP and CD3 optical density measurements were made to assess the spatial relationship between T cells and chronic active lesions (N=56). Perivascular cuffing was quantified at the medulla oblongata of N=147 MS donors, of which lesion activity and localization were characterized in all dissected tissue blocks.
Results: There was no difference in CD4/CD8 T cell-ratio between MS and control donors. Proportions of CD4+ and CD8+ T cells expressing the TRM cell-associated markers CD69 and CD103, among others, were similar. In situ, T cells were mostly located in the vicinity of blood vessels. There was an enrichment of T cells in chronic active compared to inactive lesions. Formation of perivascular cuffs was more frequent in progressive MS donors and correlated with an increased proportion of chronic active lesions.
Discussion: MS brain T cells display a TRM-like phenotype and are enriched in chronic active lesions. Perivascular cuff-formation is associated with more chronic active lesions and progressive disease course. T cells may play a facilitating role in the initiation or maintenance of chronic active lesions. Further correlation studies between flowcytometry and immunohistochemistry are anticipated.
Disclosure: This work was sponsored by “de Vriendenloterij” MS Research grant 14-888. Nina Fransen: nothing to disclose; Joost Smolders: received lecture and/or consultancy fee of Biogen, Merck, Sanofi-Genzyme, and Novartis; Jeen Engelenburg: nothing to disclose; Soraya van Etten: nothing to disclose; Jörg Hamann: nothing to disclose, Inge Huitinga: nothing to disclose.
Abstract: P736
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Pathology
Introduction: Genetic and pathology studies point to a central role of T cell-mediated inflammation in the pathophysiology of multiple sclerosis (MS). Recently, we showed the human brain to be populated by tissue resident memory T (TRM) cells.
Objectives: We explored the distribution of TRM cell markers on white matter-derived T cells of MS brain donors, and explored correlations between T cells and the presence of chronic active lesions in post-mortem brain tissue.
Methods: From brain donors of the Netherlands Brainbank with MS (n=5) and without MS (n=12), cells were isolated from normal appearing white matter acquired during rapid post-mortem autopsies, and analyzed with flowcytometry. Immunohistochemistry for HLA-PLP and CD3 optical density measurements were made to assess the spatial relationship between T cells and chronic active lesions (N=56). Perivascular cuffing was quantified at the medulla oblongata of N=147 MS donors, of which lesion activity and localization were characterized in all dissected tissue blocks.
Results: There was no difference in CD4/CD8 T cell-ratio between MS and control donors. Proportions of CD4+ and CD8+ T cells expressing the TRM cell-associated markers CD69 and CD103, among others, were similar. In situ, T cells were mostly located in the vicinity of blood vessels. There was an enrichment of T cells in chronic active compared to inactive lesions. Formation of perivascular cuffs was more frequent in progressive MS donors and correlated with an increased proportion of chronic active lesions.
Discussion: MS brain T cells display a TRM-like phenotype and are enriched in chronic active lesions. Perivascular cuff-formation is associated with more chronic active lesions and progressive disease course. T cells may play a facilitating role in the initiation or maintenance of chronic active lesions. Further correlation studies between flowcytometry and immunohistochemistry are anticipated.
Disclosure: This work was sponsored by “de Vriendenloterij” MS Research grant 14-888. Nina Fransen: nothing to disclose; Joost Smolders: received lecture and/or consultancy fee of Biogen, Merck, Sanofi-Genzyme, and Novartis; Jeen Engelenburg: nothing to disclose; Soraya van Etten: nothing to disclose; Jörg Hamann: nothing to disclose, Inge Huitinga: nothing to disclose.