Immune control of Epstein-Barr virus in MS

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Investigator

Co-investigator

Funding

  • Project Grant - $390,000 for 2013 – 2015
  • With support from Foundation 5 Million Plus and The Trish MS Research Foundation

Summary

A large body of evidence indicates that infection with Epstein-Barr virus (EBV) has a role in MS. Prof Pender has shown that people with MS have decreased immunity to EBV which could allow the accumulation of EBV-infected cells in the brain and the subsequent development of MS. This project will look at specific immune cells involved with the response to EBV infection known as CD8 T cells.

The first stage will characterise the CD8 T cell response to EBV-infected cells and investigate the role of other factors such as genetics in the altered EBV response in MS. This will hopefully lead to knowledge regarding the cause of this lower immunity against EBV in people with MS. The second stage will determine whether the alterations in the EBV immune response increases as the duration of MS increases. The final stage will determine the relationship between the CD8 T cells and other factors related to the level of EBV infection.

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

Progress to Date

Professor Pender has been able to show that the deficiency in CD8 T cells in people with MS is specifically due to reduced numbers of a sub-group of CD8 T cells called CD8 effector memory T cells. These cell types retain a memory of pathogens that they have ‘seen’ before and can immediately mount a response to clear infected cells.

 

Professor Pender has also examined blood samples from a large number of people with all forms of MS including the earliest signs of MS, known as Clinically Isolated Syndrome (CIS). The CD8 effector memory cell deficiency is present in all of these stages and types of the disease, including the very earliest stage, CIS, suggesting that is a cause, rather than a consequence, of the disease. He has also shown that other T cell types are also decreased over the course of disease, contributing to overall T cell exhaustion.

 

Professor Pender will continue to tease apart the mechanism by which this deficiency may lead to inadequate control of EBV infection, and how this may lead to MS. Professor Pender will also look at the relationship between MS and different phases of EBV infection as well as the immune response to EBV infection.

 

This work is vitally important for the development of new therapies aimed at preventing and treating MS by controlling EBV infection. An exciting development in this direction was revealed earlier this year, when Professor Pender and his colleagues published the promising results for a patient with secondary progressive MS who was treated with CD8 cells primed to recognise EBV. The therapy had no adverse effects and the patient showed clinical improvement with reduced disease activity. This is the first time that this type of therapy, known as adoptive immunotherapy, has been used to treat MS or any other autoimmune disease. Professor Pender and colleagues are now planning to undertake a phase I clinical trial of the therapy.

 

Publications

  • Pender MP, Burrows SR (2014) Epstein–Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clinical & Translational Immunology 3:e27.
  • Pender MP, Csurhes PA, Smith C, Beagley L, Hooper KD, Raj M, Coulthard A, Burrows SR, Khanna R (2014a) Epstein–Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Multiple Sclerosis Journal 20:1541–1544. Clinical Commentary in: Multiple Sclerosis Journal 20:1545.
  • Pender MP, Csurhes PA, Pfluger CMM, Burrows SR (2014b) Deficiency of CD8+ effector memory T cells is an early and persistent feature of multiple sclerosis. Multiple Sclerosis Journal 20:1825–1832.
  • Pender MP, Khanna R (2014) Epstein–Barr virus-specific adoptive immunotherapy: a new horizon for multiple sclerosis treatment? Immunotherapy 6:659–661. 

Updated 13/04/2015