EBV-activated CD8+ Tcells infiltrate the MS brain

A forum to discuss research on the origins of MS and its development.
Post Reply
User avatar
frodo
Family Elder
Posts: 1342
Joined: Wed Dec 02, 2009 3:00 pm
Contact:

EBV-activated CD8+ Tcells infiltrate the MS brain

Post by frodo » Tue Oct 08, 2019 2:26 am

More clues pointing to EBV as the culprit. And more evidence that EAE (a CD4+ disease) and MS have nothing to do.

EBV-activated CD8+ Tcells infiltrate the MS brain and interact locally with virus infected cells.

https://jvi.asm.org/content/early/2019/ ... 9.abstract

IMPORTANCE

EBV establishes a lifelong and asymptomatic infection in most individuals and more rarely causes infectious mononucleosis and malignancies, like lymphomas. The virus is also strongly associated with MS, a chronic neuroinflammatory disease with unknown etiology. Infectious mononucleosis increases the risk of developing MS and immune reactivity toward EBV is higher in persons with MS indicating inadequate control of the virus.

Previous studies have suggested that persistent EBV infection in the CNS might stimulate an immunopathological response causing bystander neural cell damage. To verify this, we need to identify the immune “culprits” responsible for the detrimental antiviral response in the CNS.

In this study, we analyzed postmortem brains donated by persons with MS and show that CD8 cytotoxic T cells recognizing EBV enter the brain and interact locally with the virus infected cells. This antiviral CD8 T cell-mediated immune response likely contributes to MS pathology.

User avatar
frodo
Family Elder
Posts: 1342
Joined: Wed Dec 02, 2009 3:00 pm
Contact:

Re: EBV-activated CD8+ Tcells infiltrate the MS brain

Post by frodo » Tue Oct 08, 2019 2:31 am

And maybe the mechanism by which the anti-EBV Tcells cause inflammation is because they cross-react with myelin MBP:

Myelin-specific CD8 T cells exacerbate brain inflammation in CNS autoimmunity

https://www.jci.org/articles/view/132531

Image

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS. Although CD4 T cells are implicated in MS pathogenesis and have been the main focus of MS research using the animal model experimental autoimmune encephalomyelitis (EAE), substantial evidence from patients with MS points to a role for CD8 T cells in disease pathogenesis.

We previously showed that an MHC class I-restricted epitope of myelin basic protein (MBP) is presented in the CNS during CD4 T cell-initiated EAE. Here, we investigated whether naïve MBP-specific CD8 T cells recruited to the CNS during CD4 T cell-initiated EAE engaged in determinant-spreading and influenced disease.

We found that the MBP-specific CD8 T cells exacerbated brain but not spinal cord inflammation. We show that a higher frequency of monocytes and monocyte-derived cells presented the MHC class I-restricted MBP ligand in the brain compared to the spinal cord.

Infiltration of MBP-specific CD8 T cells enhanced ROS production in the brain only in these cell-types and only when the MBP-specific CD8 T cells expressed Fas ligand (FasL).

These results suggest that myelin-specific CD8 T cells may contribute to disease pathogenesis via a FasL-dependent mechanism that preferentially promotes lesion formation in the brain.

Post Reply
  • Similar Topics
    Replies
    Views
    Last post