Dr Ian Humphreys, School of Medicine, and a Wellcome Trust Career Development Fellow believes that the findings will have important implications for the design of vaccines to combat viral pathogens.
Lymphocytes (red), comprising natural killer cells and T cells, migrating between and through cultured endothelial cells (outlined in green). Credit: Dr David Becker, Wellcome Images.
Cytokines are molecules produced by cells of the immune system to orchestrate the inflammatory response. The cytokine IL-10 is generally regarded as having a suppressive effect, largely because it dampens the activity of another population of immune cells known as T cells that act during the later stages of infection. This is important because excessive T cell responses can result in damage to healthy tissues.
Natural Killer (NK) cells are the body’s first line of defence against viruses and are essential for keeping virus-infected cells in check while T cells prepare to attack.
The new University research has found that rather than suppress the NK cell response, in fact IL-10 has the opposite effect.
Dr Ian Humphreys, School of Medicine, who led the study, said: “We were surprised to see that IL-10 had a positive effect on NK cell survival. Our results suggest that, IL-10 prevents a suicide mechanism known as Activation Induced Cell Death.
“Therefore, not only does IL-10 limit bystander damage during acute infections, it can actually help the early antiviral NK cell response”
Activation Induced Cell Death is the process by which cells of the immune system commit suicide if they are activated for too long. It provides a feedback mechanism to prevent the continued expansion of a cell population and is important for the resolution of an immune response.
When the team blocked the ability of NK cells to respond to IL-10, they found that large numbers of cells committed suicide even in the presence of other cytokines that are known to promote NK cell proliferation.
“The findings reveal a dimension of the anti-virus immune responses that had not previously been appreciated. Cytokines and their inhibitors are increasingly being exploited clinically to manage inflammatory disease. How this fits into the bigger picture is not yet clear, but it implies that manipulating IL-10 may be useful in the treatment of acute viral infections in terms of controlling the virus and limiting infection-induced pathology,” added Dr Humphreys
“We are now investigating the effect that IL-10 has on human NK cell responses to the pathogenic human herpesvirus cytomegalovirus.”
The findings were published in the Journal of Immunology.