A research team led by Professor Eui-Cheol Shin and Professor Su-Hyung Park from the Graduate School of Medical Science and Engineering has discovered a mechanism of tissue damage in acute viral infections, specifically in acute hepatitis A (AHA) patients. The researchers identified a group of cells, known as bystander immune cells, as one of the major causes of liver tissue damage in infected patients. This research was published in the January issue of the scientific journal Immunity.

Viral infections typically destroy human cells by replication. Viruses infect and hijack host cells to produce copies of themselves, which causes the host cell to lyse. To fight off this kind of infection, our immune system launches a sophisticated response, mainly facilitated by different types of white blood cells such as macrophages, T cells, and B cells. These immune cells specific to the virus may act as alarms when they recognize foreign bodies, produce antibodies that bind to the viral receptors, or kill the virus directly.

However, some cases deviate from this known mechanism. The research team observed that in AHA-infected patients, HAV-specific CD8+ T cells were activated, but CD8+ T cells specific to other viruses — known as bystander cells — were also activated. The team analyzed blood samples of AHA patients, provided by Chung-Ang University Hospital. The researchers isolated the immune cells and analyzed how the cell physiology and function differ from healthy controls using flow cytometry assays. They found that the HAV-infected cells release cytokines called IL-15, and that these activate the bystander cells. The bystander immune cells target the virus-infected cells through receptors called NKG2D and NKp30, causing tissue damage in the patient.

This research was the first to describe the clinical significance of bystander immune cells in viral diseases. Hoyoung Lee — a graduate student in the Biomedical Science and Engineering Interdisciplinary Program and one of the co-first authors of the paper — mentioned that this study has been part of a neglected field of immunology. The research shed new light on the mechanism of tissue damage in viral infections and had significant therapeutic implications. Lee said that the team hopes to ultimately invent a therapeutic application that can block these mechanisms to abolish tissue damage in viral infections and hopefully in other immune diseases where tissue damage is found as well.

The researchers are now working on elucidating the cellular and molecular mechanisms in the bystander CD8+ T cells such as cell signaling, gene regulation, and other mechanisms that turn them into harmful cells. Currently, they are working on healthy CD8+ T cells and trying to replicate the observed phenomenon in bystander cells to further understand this phenomenon.