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Abstract
Myelin-reactive T cells have been identified in patients with multiple sclerosis (MS) and healthy subjects with comparable frequencies, but the contribution of these autoreactive T cells to disease pathology remains unknown. A total of 13,324 T cell libraries generated from blood of 23 patients and 22 healthy controls were interrogated for reactivity to myelin antigens. Libraries derived from CCR6+ myelin-reactive T cells from patients with MS exhibited significantly enhanced production of interferon-γ (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to healthy controls. Single-cell clones isolated by major histocompatibility complex/peptide tetramers from CCR6+ T cell libraries also secreted more proinflammatory cytokines, whereas clones isolated from controls secreted more IL-10. The transcriptomes of myelin-specific CCR6+ T cells from patients with MS were distinct from those derived from healthy controls and, notably, were enriched in T helper cell 17 (TH17)–induced experimental autoimmune encephalitis gene signatures, and gene signatures derived from TH17 cells isolated other human autoimmune diseases. These data, although not causal, imply that functional differences between antigen-specific T cells from MS and healthy controls are fundamental to disease development and support the notion that IL-10 production from myelin-reactive T cells may act to limit disease progression or even pathogenesis.
Via Krishan Maggon
Vol. 7, Issue 287, p. 287ra74
Sci. Transl. Med. DOI: 10.1126/scitranslmed.aaa8038RESEARCH ARTICLE
MULTIPLE SCLEROSIS
Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosisYonghao Cao1,*, Brittany A. Goods2,*, Khadir Raddassi1, Gerald T. Nepom3, William W. Kwok3,4,J. Christopher Love5,6,† and David A. Hafler1,6,†,‡+Author Affiliations
1Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.2Department of Biological Engineering, Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.3Benaroya Research Institute, Virginia Mason Research Center, Seattle, WA 98101, USA.4Department of Medicine, University of Washington, Seattle, WA 98101, USA.5Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.6The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.+Author Notes
↵* These authors contributed equally to this work.
↵† These authors contributed equally to this work.
↵‡Corresponding author. E-mail: david.hafler@yale.eduThe Yale-led team analyzed T cell populations from 23 MS patients and 22 healthy controls. Existing drugs target the MS-specific cytokines identified in the study and should be a promising new treatment for the disease, the authors say.
http://news.yale.edu/2015/05/13/yale-researchers-solve-multiple-sclerosis-puzzle