Now that we know what PD-1 is, it's time to look at this paper
Cencioni MT, Magliozzi R, Nicholas R, Ali R, Malik O, Reynolds R, Borsellino G, Battistini L, Muraro PA. Programmed death 1 (PD1) is highly expressed on CD8+ CD57+ T cells in patients with stable multiple sclerosis and inhibits their cytotoxic response to Epstein-Barr virus. Immunology. 2017. doi: 10.1111/imm.12808. [Epub ahead of print]
We know that virtually everybody with MS is infected with Epstein Barr Virus. Most people are as it is very common in humans.
We get infected through saliva. It then infects B cells and makes them proliferate like crazy and turn into memory B cells. The virus then shuts down and hides in the B cell, where it is not going to do much damage. But every now and then the virus activates, and sheds live virus. The immune response recognises the virus and kills the infected B cells and things all quieten down.
In Australia they are making T cells that will kill EBV, based on a very small, unreproduced study stating that it may influence the activity of MS.
MS and the CD8 that attack anti-EBV viral T cells
A subset of CD8 cells express CD57 - which is
an enzyme - (Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1-B3GAT1) that recognises sugar molecules and is involved in the destruction of chemicals, and I guess viruses.
In healthy individuals they killed EBV infected cells but in stable MS these cells also expressed PD-1, suggesting that they had become immunologically exhausted so they were not killers, but in active MS the CD8 cells had PD-1 and were killing.
This suggested that when MS is stable they do not control the EBV infection, maybe because it is at a silent stage, but this may enable the re-activation of virus, which could trigger disease.
Is the disease caused by the attack of virus?.
The question is, is it a cause or really a consequence?
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the central nervous system of patients with multiple sclerosis (MS) as a possible cause of disease. We have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 patients with MS 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 immunoglobulin-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 patients with MS compared with active patients with MS 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 patietns with MS during remission may be one factor preceding and enabling the reactivation of the virus in the central nervous system and may cause exacerbation of the disease.