Like tuning a violin to produce strong, elegant notes, researchers at The Wistar Institute have found multiple receptors on the outside of the body's killer immune system cells which they believe can be selectively targeted to keep the cells in superb infection- and disease-fighting condition.
In a study published online November 30 in Nature Immunology, the researchers describe their discovery of seven different receptors on T cells that can tamp down immune responses during a prolonged battle with an infectious pathogen or against developing cancer.
Chronic over-stimulation of the immune system can lead to poor control of infections and cancer, so the results explain why it is that these key immune cells gradually become "exhausted" and ineffective over time, says the study's lead author, E. John Wherry, Ph.D., an assistant professor in Wistar's Immunology Program.
Wherry had recently been involved in discovering a single receptor involved in turning off T cells but this new study shows that at least six more receptors can also restrain or negatively regulate immune responses. According to Wherry, a key finding is that these new receptors likely control different aspects of T cell responses, such as division or expansion, controlling viral replication, and local killing of infected cells versus secretion of long-range active antiviral proteins.
"This amount of control over T cells' response is remarkable. It suggests that layers of negative regulation exist on exhausted T cells from co-expression of multiple inhibitory receptors," he says. "My bet is that these receptors inhibit different aspects of the T cells' response, but that the net result of their activation is to turn specific T cell populations off.
"We are starting to see a picture emerging of a really tuneable array of inhibitory receptors expressed on T cells," Wherry says. "That suggests it may be possible to not only dramatically enhance antiviral or antitumor T cell responses, but also to fine tune which response you want to enhance in order to reverse T cell exhaustion and continue fighting an infection or disease.
"This presents us with a great clinical opportunity," Wherry says. "T cells have a lot of weapons at their disposal to control viral infection and most of them are disarmed when these cells become exhausted. It may be possible to selectively rearm T cells while generally reinvigorating them."