Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis.
Authors | |
Keywords | |
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. |
Year of Publication | 2015
|
Journal | Sci Transl Med
|
Volume | 7
|
Issue | 287
|
Pages | 287ra74
|
Date Published | 2015 May 13
|
ISSN | 1946-6242
|
URL | |
DOI | 10.1126/scitranslmed.aaa8038
|
PubMed ID | 25972006
|
PubMed Central ID | PMC4497538
|
Links | |
Grant list | U19 AI070352 / AI / NIAID NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States
P01 AI039671 / AI / NIAID NIH HHS / United States
P01 AI045757 / AI / NIAID NIH HHS / United States
U19 AI046130 / AI / NIAID NIH HHS / United States
P01 AI073748 / AI / NIAID NIH HHS / United States
|