Natural killer (NK) cells are responsible for killing harmful cells in the body. This includes the body’s own cells that are infected with viruses, and other immune cells that inappropriately attack our own body (autoimmune cells). Previous work has suggested that in some people with MS, the killing power of NK cells is reduced. In a laboratory model of MS, this reduced function of NK cells is associated with increased MS relapses.
In this Project Grant Dr Fewings and her team will first analyse NK cells in MS in a more detailed way than has ever been conducted before, to better understand the changes in NK cells in MS. She will also determine if NK cells from people with MS are able to kill cells infected with viruses or activated immune cells (including the autoimmune cells that drive MS) in the laboratory. Of particular interest are cells infected with the Epstein Barr virus (EBV) which has been implicated in increased risk of MS.
A number of drugs that enhance the function of NK cells have been approved to treat cancer. Dr Fewings will investigate if these drugs have the potential to be repurposed for use in people with MS, to improve the function of NK cells to kill EBV- infected cells or toxic immune cells.
Dr Fewings and her team designed and developed a new test to compare different subsets of NK cells in detail. This technique (called “high dimensional flow cytometry”) involves passing blood cells past a laser that allows them to detect over 21 different properties of each cell at once, combined with a complex analysis pipeline. This work has led to multiple collaborations with other researchers who plan on using this test for other diseases. One of these collaborations is looking to link up with Professor Georges Grau to examine NK cells in response to different MS treatments.
By comparing NK cells from people with and without MS, Dr Fewings has found that numbers of a particular subset of NK cells are reduced in people with MS. This suggests that the overall “killing power” of NK cells is reduced in people with MS.
Dr Fewings has also generated a model system of EBV infection in the laboratory, where she can drive the EBV-infected cells to be susceptible to killing by NK cells. Her team is generating a large bank of EBV-infected cells, with matching NK cells also collected. Going forward, they will use this system to see whether NK cells from people with MS have reduced capacity to kill EBV-infected cells, and whether the killing capacity can be restored using current cancer therapies. If successful, this could inform the development of new therapies.
This work has been presented at several national and international conferences, and a manuscript is being prepared for publication in a scientific journal.
Updated 31 March 2022
Updated: 05 January, 2018