Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Name
Love_Distinct inlammatory.pdf
Size
997.43 KB
Format
Adobe PDF
Checksum (MD5)
d4ec0eb41bedd7c0fd85b9667cafa881
Author(s)
Cao, Y.
Raddassi, K.
Nepom, G. T.
Kwok, W. W.
Goods, Brittany A.
Love, John C
Hafler, David A.
Date Issued
March 2015
Journal
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
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.
MIT Department
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 MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/scitranslmed.aaa8038
