Defective T-cell control of EBV infection in multiple sclerosis

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.

 

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.

 

I suffer from hippocampal sclerosis with atrophy. Is it a milder version of MS ? My fatigue started only after this.

 

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