Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Author(s)
Cao, Y.; Raddassi, K.; Nepom, G. T.; Kwok, W. W.; Goods, Brittany A.; Love, John C; Hafler, David A.; ... Show more Show less![Thumbnail](/bitstream/handle/1721.1/109452/Love_Distinct%20inlammatory.pdf.jpg?sequence=4&isAllowed=y)
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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.
Date issued
2015-03Department
Broad Institute of MIT and Harvard; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering; Koch Institute for Integrative Cancer Research at MITJournal
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Cao, Y.; Goods, B. A.; Raddassi, K.; Nepom, G. T.; Kwok, W. W.; Love, J. C. and Hafler, D. A. “Functional Inflammatory Profiles Distinguish Myelin-Reactive T Cells from Patients with Multiple Sclerosis.” Science Translational Medicine 7, no. 287 (May 13, 2015): 287ra74 © 2015 American Association for the Advancement of Science (AAAS)
Version: Author's final manuscript
ISSN
1946-6234
1946-6242