“We were interested in trying to understand why so many viral infections are associated with neurological diseases,” says Elizabeth Balint, a Ph.D. student at McMaster who led the study with Ali Ashkar, a professor with the Department of Medicine and the Canada Research Chair in Natural Immunity and NK Cell Function. “Our evidence suggests that it’s not the virus itself that causes the damage, but a unique population of T cells which are part of the immune system, that are actually responsible for the damage.”
The research team from McMaster started by putting their focus on the Zika virus, and during laboratory testing, they found that T cells specific to Zika were designed to eliminate infected cells. However, that is not all that they found.
“What was interesting in our study is that although we did find some T cells specific for Zika, we identified cells that weren’t functioning like a normal T cell and were killing lots of cells that weren’t infected with Zika,” says Balint.
NKG2D+CD8+ T cells have an aggressive immune system response, and according to the researchers, these cells are responsible for neurological damage experienced from infections beyond the Zika virus, such as septic shock and SARS-CoV-2. The aggressive response is the result of large amounts of inflammatory cytokine proteins being produced in the body. When produced in moderation they help the body to coordinate the immune responses to fight infection or injury by telling immune cells where to go and what to do when they get there.
However, when in excess, even something that is meant to be good can be bad. These findings offer new paths and targets for treatments of neurological diseases that are the results of viral infections, and Balint may have already found a promising treatment which she hopes to continue working towards, building on this research, to find a treatment that could be used in humans.
“If our body’s immune cells overreact and overproduce inflammatory cytokines, this condition will lead to non-specific activation of our immune cells which in turn leads to collateral damage. This can have severe consequences if it happens in the brain,” Ashkar says.
“Elizabeth has experimented with an antibody that can completely block and treat devastating neurotoxicity in the animal model, which is already in clinical trials for different uses in humans,” says Ashkar.
“There are a few different other viruses we’re interested in studying, which will aid us in creating the best treatment options,” Balint says.
Funding for this study was provided by the Canadian Institutes of Health Research. Balint is also a recipient of a Canada Graduate Scholarship Doctoral Award.
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