A team of doctors in New York is attempting to learn more about the immune system's role in the liver damage associated with hepatitis C. In that way, they say, better treatments could be designed for people with the disease. While such treatments may still be years away, a new study unveiled in early April1 may be the basis for such a discovery.
Immunological Focus
In their study, Dan Littman, MD, PhD, in the Molecular Pathogenesis Program at the Skirball Institute of Biomolecular Medicine at New York University School of Medicine and his fellow researchers focused on natural killer T (NKT) cells. These are the immune system's sentinels, patrolling the intricate blood vessels of the liver for invaders or signs of tissue damage. They patrol even in the face of blood flow and halt only when they receive a chemical signal to unleash an immune system assault on viruses, bacteria and other microbes.
NKT cells are also responsible for the inflammation and cell death that occurs in the liver when hepatitis strikes. Hepatitis, thus, is a reaction to viruses, parasites like malaria or other infections. Knowing that, strategies designed to call off NKT cells' ruthless and overwhelming attacks could be the basis for an effective hepatitis treatment, Littman and his team point out.
Filling the Information Gap
Not much was known about the role of NKT cells in the liver prior to this study, they said. Though medical experts have been aware of these immunological cells' prevalence in the liver—more so than in any other organ—little was understood about how they accomplish the task of immune surveillance. Since the blood vessels that intertwine throughout the liver carry a cornucopia of nutrients, toxins, proteins, lipids and other substances, NKT cells must tolerate these foreign molecules while still being effective at responding to infection.
"It wasn't clear how NKT cells survey [tissue], or even if they survey at all," explained Littman, who is also a professor of Molecular Immunology and of Pathology and Microbiology at NYU.
A 'Startling Discovery'
To better visualize the activity of these immune cells, the research team used mice in which the cells were labeled with a fluorescent marker that made them stand out using a form of gene manipulation. The investigators then closely followed their activity.
"The startling discovery was that these NKT cells just move within the sinusoids [vascular passages] intravascularly," Littman stated. In contrast, he said, immune cells in the lymph nodes and spleen monitor for infections within specialized compartments that shield them from the turmoil of the bloodstream. "In this case, it looks like NKT cells are doing their surveillance from within the vessels," he said.
The observations showed that NKT cells in the liver crawl randomly within the sinusoids, even upstream against blood flow, passing one another and even changing direction, Littman explained. "It is very different from the kind of classical mechanism of lymphocytes rolling through vessels with the blood flow and when they are activated, coming to a stop, and then crossing through vessel walls in response to a signal," he said.
Other Distinct Behaviors
The investigators also noticed that the roving NKT cells in the liver stopped when they were alerted to a foreign organism. The cells then call up other inflammatory cells that destroy the invading pathogen and may also help repair the damage that was subsequently caused, said Littman.
These cells' role in triggering hepatitis may be of value clinically, Littman added. "In general, these NKT cells could have an important inflammatory role, particularly in the case of chronic hepatitis. If that is the case, we speculate that it may be possible to manipulate the NKT cell … to ameliorate the inflammatory process."
1. Geissman F, Cameron TO, Sidobre S et al. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol 2005 Apr;3(4):e113. Epub 2005 Apr 5.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
