Evidence has long suggested multiple sclerosis (MS) is an autoimmune disease, but researchers have been puzzled because they found the same T cells that attack the myelin sheathing around nerve cells in MS patients are present in healthy subjects as well.
Now researchers from the Yale School of Medicine and colleagues at the Massachusetts Institute of Technology (MIT) report that auto-reactive T cells in MS patients produce different types of inflammatory hormones called cytokines than they do in healthy subjects.
"In most people, these T cells are acting to repair tissue, but in MS patients, they do damage to the nervous system," said Dr. David Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and senior author of the study, published May 14 in the journal Science Translational Medicine.
The 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.
FUNCTIONAL INFLAMMATORY PROFILES DISTINGUISH MYELIN-REACTIVE T CELLS FROM PATIENTS WITH MULTIPLE SCLEROSIS
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.
Sci Transl Med 13 May 2015:
Vol. 7no. 287 pp. 287ra74DOI:10.1126/scitranslmed.aaa8038
Now researchers from the Yale School of Medicine and colleagues at the Massachusetts Institute of Technology (MIT) report that auto-reactive T cells in MS patients produce different types of inflammatory hormones called cytokines than they do in healthy subjects.
"In most people, these T cells are acting to repair tissue, but in MS patients, they do damage to the nervous system," said Dr. David Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and senior author of the study, published May 14 in the journal Science Translational Medicine.
The 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.
FUNCTIONAL INFLAMMATORY PROFILES DISTINGUISH MYELIN-REACTIVE T CELLS FROM PATIENTS WITH MULTIPLE SCLEROSIS
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.
Sci Transl Med 13 May 2015:
Vol. 7no. 287 pp. 287ra74DOI:10.1126/scitranslmed.aaa8038
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