Abstract Details

Title Increased Frequencies of Myelin Reactive CCR6+ Pathogenic IL-17/GM-CSF/IFN? Secreting CD4+ T Cells in Patients with Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 225

Objective

Background BACKGROUND: MS is a genetically mediated autoimmune disease characterized by infiltration of immune cells in the CNS resulting in demyelination. It was recently shown that IL-17 secreting CD4 cells could be divided into inflammatory GM-CSF/IFN? as opposed to IL-10 secreting subsets. Moreover, recent work in MS models indicates that the pathogenic myelin reactive CD4 cells secrete IL-17, GM-CSF, and IFN? while IL-10 secreting myelin reactive cells are protective.

Design/Methods DESIGN/METHODS: Using a newly described amplified T library assay, CD4 cells were sorted into naive, CCR6- and CCR6+ memory populations and seeded at 2,000 cells/well in 96-well plates followed by stimulation with PHA and IL-2 in the presence of irradiated allogeneic feeder cells for 2 weeks. The frequencies of myelin (MOG, PLP and MBP) antigen-specific T cells and cytokine profiling were measured after cells were re-stimulated by autologous monocytes and peptides for another 5 days.

Results RESULTS: The frequency of myelin-specific autoreactive CD4 T cells characterized by the secretion of the inflammatory cytokines IFN? (MS vs controls, 236.4 ± 4.21 vs 154.1 ± 9.37 pg/ml), IL-17 (155.5 ± 10.31 vs 3.6 ± 0.49 pg/ml), and GM-CSF (25.4 ± 5.74 vs 10.2 ± 3.23 pg/ml) was increased in patients with MS compared to healthy control subjects. These CD4 T cells resided in CCR6+ memory CD4 T cell compartment. Moreover, in age-matched healthy controls, the myelin reactive CD4 cells secreted the anti-inflammatory IL-10 (15.8 ± 1.38 vs 32.2 ± 5.99 pg/ml).

Conclusions CONCLUSIONS: Pathogenic IL-17/GM-CSF/IFN?-secreting autoreactive CD4 T cells are more prevalent in patients with MS while myelin reactive CD4 cells secrete IL-10 in healthy subjects.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
David A. Hafler, MD, FAAN (Yale University School of Medicine, Dept of Neurology)	Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genetech. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Hafler has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Joint Commission International.
Crystal Watson (Atara Biotherapeutics)	Ms. Watson has received personal compensation for serving as an employee of Atara Biotherapeutics. Ms. Watson has received stock or an ownership interest from Atara Biotherapeutics.

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