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MS is an immune mediated neurological disease where the immune system inappropriately attacks the brain and spinal cord, which can lead to multiple impairments. Regulatory T cells (Tregs) are responsible for controlling the immune cells, known as effector T cells, that cause these attacks. However, in MS, Tregs are unable to control these effector T cells. In addition, there is evidence that the effector T cells that attack the brain and spinal cord in MS have acquired mechanisms so that they can no longer be controlled by Tregs. Therefore, there are two levels of dysfunction: Tregs that cannot stop effector T cells, and effector T cells that resist being stopped by Tregs. This leads to uncontrolled attacks on the brain and spinal cord.
This project investigated whether these Tregs have normal function in clinically isolated syndrome (CIS), the precursor of MS, and whether they can control the immune cells that attack the brain. This will help identify how early this immune imbalance occurs and inform us as to how MS begins, allowing us to develop strategies to prevent CIS from progressing to MS.
Dr Kaskow and her team found that immune dysregulation is present early in the MS disease course in CIS and that both the Tregs and effector T cells are dysfunctional. They also found that IL-33, a molecule that is known to regulate immune responses, was able to restore this immune dysfunction.
The team also discovered that Tregs from people living with MS treated with natalizumab (Tysabri) were more effective at controlling effector T cells compared to those without MS. This suggests that natalizumab may enhance the immune response beyond its role in blocking the entry of immune cells into the brain.
This work has shed light on the role of Tregs early in the MS disease course, which may pave the way for development of strategies to prevent progression from CIS to clinically definite MS.
Future work will include increasing the number of T cell samples, as well as investigating samples from individuals over time who have progressed from a CIS diagnosis to clinically definite MS and individuals treated with other disease-modifying therapies.
Updated 31 July 2024
Dr Belinda Kaskow
$16,000
2022
1 year
Current project
