CD8 response to EBV

Programmed death 1 is highly expressed on CD8+CD57+ T cells in patients with stable multiple sclerosis and inhibits their cytotoxic response to EBV.Cencioni MT, Magliozzi R, Nicholas R, Ali R, Malik O, Reynolds R, Borsellino G, Battistini L, Muraro P.

Immunology.  doi: 10.1111/imm.12808. [Epub ahead of print]

Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the CNS of patients with Multiple Sclerosis (pwMS) as a possible cause of disease. In this study, we have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 pwMS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death-1 (PD-1) and human inhibitor receptor Ig-like transcript 2 (ILT2). We demonstrate that polyfunctional cytotoxic CD8+CD57+ T cells are able to kill EBV-infected cells in healthy donors. In contrast, an anergic exhaustion-like phenotype of CD8+CD57+ T cells with high expression of PD-1 was observed in inactive pwMS compared with active pwMS or healthy donors. Detection of CD8+CD57+ T cells in meningeal inflammatory infiltrates from post-mortem MS tissue confirmed the association of this cell phenotype with the disease pathological process. The overall results suggest that ineffective immune control of EBV in pwMS during remission may be one factor preceding and enabling the reactivation of the virus in the CNS and may cause exacerbation of the disease.

So some work from the other side of “The Smoke”- crap name for London as we haven’t had any pea soupers (lots of Smog) in years. This points the finger at Cd8 T cells as important tools to kill EBV infected cell. In MS maybe the MS killing mechanism aren’t that great. Is this the essential important issue.

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  • Think it was "The Big Smoke". It did used to be filthy. Edinburgh was "Auld Reekie". Nothing crap about the names – just part of history.

  • "we have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 pwMS in active and inactive disease"

    Do they mean in midst of relapse for active disease ?..because isn't ms always active unless under NEDA via therapy DMT

  • This is an absolute gem of a find MD, thank-you! Can you either "transplant" (from donors) or turn on these cytotoxic pd-1 negative CD8 CD57 T-cells in an MS patient? Or turn off these anergic pd-1+ CDB CD57 T-cells in an MS patient? How does one measure effects of these cytoxic donor pd-1 negative CD8 CD57 cells from donors (non MS patient) on EBV-driven B-cells in follicles in the brain in vivo and not post-mortem?

    I am surprised that the MS world of research is not more excited about this paper. It supports Dr. Pender's work and fits with Dr. G's hypothesis on the cause and progression of MS if one were to believe that EBV driven B-cells are the cause of MS and its progression.

    • Nissan perhaps the scientific community is still "afraid" to embrace EBV as a potential causer or propellant of MS because many pwMS test exams for EBV serology, I think most use ELISA, and it points out false negative results.
      The problem would be in the detection? Most likely.

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