Defective T-cell control of EBV infection in multiple sclerosis

pattismith

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Defective T-cell control of Epstein–Barr virus infection in multiple sclerosis

Published online 20 January 2017

Michael P Pender, Peter A Csurhes, Jacqueline M Burrows and Scott R Burrows

Abstract

Mounting evidence indicates that infection with Epstein–Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS).

Defective elimination of EBV-infected B cells by CD8+ T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain.

Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects. In 20 HLA-A2+ healthy subjects and 20 HLA-A2+ patients we also analysed CD8+ T cells specific for individual peptides, measured by binding to HLA-peptide complexes and production of IFN-γ, TNF-α and IL-2.

We found a decreased CD8+ T-cell response to EBV lytic, but not CMV lytic, antigens at the onset of MS and at all subsequent disease stages.

CD8+ T cells directed against EBV latent antigens were increased but had reduced cytokine polyfunctionality indicating T-cell exhaustion.

During attacks the EBV-specific CD4+ and CD8+ T-cell populations expanded, with increased functionality of latent-specific CD8+ T cells.

With increasing disease duration, EBV-specific CD4+ and CD8+ T cells progressively declined, consistent with T-cell exhaustion.

The anti-EBNA1 IgG titre correlated inversely with the EBV-specific CD8+ T-cell frequency.

We postulate that defective CD8+ T-cell control of EBV reactivation leads to an expanded population of latently infected cells, including autoreactive B cells.
 

Tammy

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Mounting evidence indicates that infection with Epstein–Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS).
I agree................and that's why there are so MANY overlapping symptoms of CFS and MS. With some cases of aggressive MS, I believe it's because of a more aggressive strain of EBV.
 

ljimbo423

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United States, New Hampshire
To investigate the relationship between the EBV DNA load in the blood and the EBV-specific T-cell response, we employed real-time PCR with primers and probe directed towards a conserved portion of the BamH1W segment of the EBV genome36 in DNA extracted from the same PBMC sample used to study the T-cell response in 24 of the healthy EBV-seropositive subjects and 50 of the MS patients. The median EBV DNA copy number in the PBMC in the patients (2μg−1 of DNA) did not differ significantly from that in the healthy controls (2.5μg−1 of DNA) (P=0.564) (Figure 6a), consistent with most previous studies.2 In the patients with MS the EBV load increased as the LCL-specific CD8+ T-cell frequency decreased (Figure 6b), although the correlation did not reach statistical significance (r=−0.19, P=0.148)

I think this study shows immune system dysfunction causing high EBV titers, not increased viral load. The PCR testing for viral load is not "statistically significant".

Jim
 
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