Les celulles T autoréactives des patients atteints de myasthénie sont caractérisées par l'augmentation de l' IL-17,...

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Les celulles T autoréactives des patients atteints de myasthénie sont caractérisées par l'augmentation de l' IL-17,...

Message par Pboulanger » 30 janv. 2016 11:48

:hi:

Lu sur "The journal of immunology " http://www.jimmunol.org/content/early/2 ... 9.abstract

cette publication intitulée Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production
(en français Les celulles T autoréactives des patients atteints de myasthénie sont caractérisées par l'augmentation de l' IL-17, l'IFN-γ, et GM-CSF et par la diminution de la production d'IL-10.)

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Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production

Yonghao Cao*,†, Robert A. Amezquita†, Steven H. Kleinstein†,‡,§, Panos Stathopoulos*, Richard J. Nowak* and Kevin C. O’Connor*

*Department of Neurology, Yale School of Medicine, New Haven, CT 06511;
†Department of Immunobiology, Yale School of Medicine, New Haven, CT 06511;
‡Department of Pathology, Yale School of Medicine, New Haven, CT 06511; and
§Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511

Address correspondence and reprint requests to Dr. Kevin C. O’Connor and Dr. Yonghao Cao, Yale School of Medicine, 300 George Street, Room 353, New Haven, CT 06511. E-mail addresses: kevin.oconnor{at}yale.edu (K.C.O.) and yonghao.cao{at}yale.edu (Y.C.)



Abstract


Myasthenia gravis (MG) is a prototypical autoimmune disease that is among the few for which the target Ag and the pathogenic autoantibodies are clearly defined.

The pathology of the disease is affected by autoantibodies directed toward the acetylcholine receptor (AChR). Mature, Ag-experienced B cells rely on the action of Th cells to produce these pathogenic Abs.

The phenotype of the MG Ag-reactive T cell compartment is not well defined; thus, we sought to determine whether such cells exhibit both a proinflammatory and a pathogenic phenotype.

A novel T cell library assay that affords multiparameter interrogation of rare Ag-reactive CD4+ T cells was applied.
Proliferation and cytokine production in response to both AChR and control Ags were measured from 3120 T cell libraries derived from 11 MG patients and paired healthy control subjects. The frequency of CCR6+ memory T cells from MG patients proliferating in response to AChR-derived peptides was significantly higher than that of healthy control subjects.
Production of both IFN-γ and IL-17, in response to AChR, was also restricted to the CCR6+ memory T cell compartment in the MG cohort, indicating a proinflammatory phenotype.

These T cells also included an elevated expression of GM-CSF and absence of IL-10 expression, indicating a proinflammatory and pathogenic phenotype. This component of the autoimmune response in MG is of particular importance when considering the durability of MG treatment strategies that eliminate B cells, because the autoreactive T cells could renew autoimmunity in the reconstituted B cell compartment with ensuing clinical manifestations.

Footnotes


This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health Grants R01AI114780 and U19AI056363 (to K.C.O.) and a grant from the Myasthenia Gravis Foundation of America (to K.C.O.). R.A.A. is supported by a Gilliam Fellowship awarded by the Howard Hughes Medical Institute.
Amicalement,
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