The role of immunity to Epstein-Barr virus in the development of MS

Investigators

• Prof Michael Pender, University of Queensland
• A/Prof Scott Burrows, Royal Brisbane & Women’s Hospital

Funding

• $390,000 over 2010 - 2012

Summary

MS is a common chronic inflammatory disease of the brain causing progressive disability, particularly in young people. Prof Pender and his colleagues have recently shown that people with MS have impaired immunity to the Epstein-Barr virus (EBV), which could allow the accumulation of EBV-infected cells in the brain and the subsequent development of MS.

This project will investigate the role of impaired immunity to EBV in the development of MS and will lay the foundation for preventing and curing MS by controlling EBV infection.

Progress to date

Prof Michael Pender, working at the University of Queensland, and A/Prof Scott from Royal Brisbane & Women’s Hospital, were awarded a project grant in 2010 to study the role of Epstein-Barr Virus in the development of MS.

A large body of epidemiological evidence indicates that infection with the Epstein-Barr virus (EBV), the causative agent of glandular fever, is essential for the development of multiple sclerosis (MS). EBV is a virus that selectively infects human B cells, which are the white blood cells that produce antibodies. In healthy people the number of EBV-infected B cells is kept under strict control by the immune system. Cytotoxic CD8+ T cells are the white blood cells that kill abnormal cells, such as EBV-infected B cells, and keep the number of these cells to a minimum.

In previous research studies, Prof Pender and colleagues have shown that people with MS have a decreased number of T cells capable of responding to their own EBV-infected B cells. It is thought that this decrease in the number of correct T cells might predispose people to MS by allowing the EBV-infected B cells to accumulate in the brain.

In the present project the researchers are further investigating the immune response to EBV in people with MS. They are studying the CD4+ T cell and the CD8+ T cell response to EBV to determine the cause of the decreased T cell response to EBV and its relationship to the clinical features of MS.

“In the last year we have collected blood from 79 healthy subjects and an additional 31 patients with MS for this study,” reported Prof Pender. “The blood samples have been processed and stored as serum samples, cryopreserved peripheral blood mononuclear cells (PBMC) for T cell studies and frozen PBMC for DNA studies.” The researchers are performing these studies on their new state-of-the-art Beckman-Coulter Gallios 10-colour Flow Cytometer. A Flow Cytometer is a machine that can look at larger number of cells with data collected on each individual cell. Colour-labelled antibodies are used to label the cells for markers of interest, such as CD4 and CD8.

“We have used flow cytometry to measure the proportions of T cell subsets in the peripheral blood of 68 healthy subjects and 70 patients with MS,” explains Prof Pender “The percentage of CD8+ T cells was significantly decreased whereas the percentage of CD4+ T cells and the CD4:CD8 ratio were significantly increased in patients with MS compared to healthy subjects.”

The findings confirmed the previously reported CD8+ T cell deficiency in patients with MS and showed that it contributes to the decreased CD8+ T cell response to EBV-infected B cells and worsens with age. These ground breaking finding have the potential to lead to the development of new therapies for preventing and treating MS by controlling EBV infection.

Reference

Pender MP. The essential role of Epstein–Barr virus in the pathogenesis of multiple sclerosis. The Neuroscientist published online 12 November 2010 ahead of print; DOI: 10.1177/1073858410381531.
 

Updated: 11/05/11