Monday, 20 March 2017

Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses.

Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses.Paroni M, Maltese V, De Simone M, Ranzani V, Larghi P, Fenoglio C, Pietroboni AM, De Riz MA, Crosti MC, Maglie S, Moro M, Caprioli F, Rossi R, Rossetti G, Galimberti D, Pagani M, Scarpini E, Abrignani S, Geginat J. Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses.
J Allergy Clin Immunol. 2017. pii: S0091-6749(17)30043-X. doi: 10.1016/j.jaci.2016.11.045. [Epub ahead of print]

BACKGROUND:Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that is caused by autoreactive T cells and associated with viral infections. However, the phenotype of pathogenic T cells in peripheral blood remains to be defined, and how viruses promote MS is debated.
OBJECTIVE:We aimed to identify and characterize potentially pathogenic autoreactive T cells, as well as protective antiviral T cells, in patients with MS.
METHODS:We analyzed CD4+ helper T-cell subsets from peripheral blood or cerebrospinal fluid for cytokine production, gene expression, plasticity, homing potentials, and their reactivity to self-antigens and viral antigens in healthy subjects and patients with MS. Moreover, we monitored their frequencies in untreated and fingolimod- or natalizumab-treated patients with MS.
RESULTS: TH1/TH17 central memory (TH1/TH17CM) cells were selectively increased in peripheral blood of patients with relapsing-remitting MS with a high disease score. TH1/TH17CM cells were closely related to conventional TH17 cells but had more pathogenic features. In particular, they could shuttle between lymph nodes and the CNS and produced encephalitogenic cytokines. The cerebrospinal fluid of patients with active MS was enriched for CXCL10 and contained mainly CXCR3-expressing TH1 and TH1/TH17 subsets. However, while TH1 cells responded consistently to viruses, TH1/TH17CM cells reacted strongly with John Cunningham virus in healthy subjects but responded instead to myelin-derived self-antigens in patients with MS. Fingolimod and natalizumab therapies efficiently targeted autoreactive TH1/TH17CM cells but also blocked virus-specific TH1 cells.
CONCLUSIONS: We propose that autoreactive TH1/TH17CM cells expand in patients with MS and promote relapses after bystander recruitment to the CNS, whereas TH1 cells perform immune surveillance. Thus the selective targeting of TH1/TH17 cells could inhibit relapses without causing John Cunningham virus-dependent progressive multifocal encephalomyelitis


We have been tooing and frowing between T cells and B cells and this swings back to T cells

1 comment:

  1. A similar paper, concerning Th1/Th17 cells, published in 2009, is in the US National Library of Medicine. Part of the article explains how the T cells can be re-activated by CNS antigens and progress to cause demyelination and damage to axons.

    However, of more interest is that Treg cells can suppress CD4 andTh1/Th17 reactions. So similar to the guest post by Denise Fitzgerald. (albeit with a different mode of action).

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813731/

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