Immune control of
virus in MS
Michael Pender at the University of Queensland has for many years been
researching the relationship between the Epstein Barr Virus (EBV) and the
immune system, and its role in MS. In 2013, Professor Pender and his colleague
Professor Scott Burrows received a three year project grant from MS Research
Australia, in partnership with the Trish MS Research Foundation and Foundation
5 Million Plus to continue these investigations. This project grant has
recently concluded and the researchers have achieved impressive outcomes from
their research into EBV and MS.
a large body of evidence from both Australian and international research
indicating that infection with the Epstein-Barr virus (EBV) may play a role in
the cause of MS. Around 95% of all adults have evidence of a previous EBV
infection, however, at least 99% of people with MS have had EBV.
Pender previously showed 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 aimed to build on these earlier
findings to look at specific immune cells involved with the response to EBV
infection, known as CD8 T cells.
first stage of this project Professor Pender showed 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.
Pender then examined blood samples from people with all forms of MS including
the earliest signs of MS, known as Clinically Isolated Syndrome (CIS). He found
that decreased immunity to EBV is present in all of these stages and types of
the disease, including the very early CIS stage, suggesting that EBV may be
related to the causes, rather than a consequence, of MS.
three year project, Professor Pender has made great progress into teasing apart
the mechanisms by which immune deficiency may lead to inadequate control of EBV
infection, and how this may lead to MS. He found that people with MS showed
differences in the response to both the active and latent forms of EBV. He has also
shown that other T cell types are decreased over the course of disease,
contributing to overall T cell exhaustion. Professor Pender also reported that
EBV specific CD8 T cells were not influenced by several known MS risk genes.
Pender’s work over the last decade has been highly successful and has yielded important new
insights into how and why the immune system fails to control EBV infection in
people with MS. These findings are 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 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. 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 conducting a phase I clinical trial to test the safety of
EBV specific T cell therapy in a very small group of people with progressive