New findings could inform development of treatments that manipulate immune cell activity.
Immune system cells called regulatory T cells appear to promote cytomegalovirus (CMV) latency in the spleen of mice, but suppress it in the salivary gland. Researchers at the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center presented this surprising finding in a new study in the journal PLOS Pathogens.

CMV infects over half of adults by the time they reach the age of 40. Usually, it causes no signs or symptoms, but it can be dangerous for people with weakened immune systems and for babies who contract it before birth. In most people, CMV settles into a latent state; its genome exists in the cells of the infected person, but it does not replicate or cause harm unless it is reactivated.

Previous work has shown that immune system cells known as regulatory T cells are associated with reactivation of CMV in immune suppressed patients. Whether or not regulatory T cells were causal in this context was unclear. In the new study, the research team investigated this role in mice by infecting them with a mouse version of CMV.

Eight months after infection, CMV had established latent infection of the spleen, salivary gland, lung, and pancreas. The mice were of a recently developed strain that allowed the researchers to then trigger a decrease in levels of regulatory T cells and examine the effects.

The results suggest that regulatory T cells can either suppress or reactivate latent CMV depending on where in the body they are acting. In the spleen, depletion of regulatory T cells reduced viral load and enhanced the functionality of immune cells whose job is to eliminate viruses. But opposite effects occurred in the salivary gland, suggesting that regulatory T cells normally prevent CMV reactivation and replication in the salivary gland.

Future work could explore whether these findings hold true in humans and why regulatory T cells have opposing effects in different mouse tissues. Better understanding of the role of regulatory T cells could aid development of treatments that manipulate their activity. Such treatments may hold particular promise for preventing CMV reactivation in patients with suppressed immune systems (eg those with HIV or organ–transplants), and are already being investigated in such patients.

The first author on the study is Maha Almanan, a graduate student in the laboratory of David Hildeman, PhD, Division of Immunobiology at Cincinnati Children’s. Hildeman is a corresponding author on the study.