OHSU Researchers Make Key Immune System Discovery

"This research is of particular interest to populations that are highly vulnerable to disease, such as the aging population," said Janko Nikolich-Zugich, M.D., Ph.D., a senior scientist at the Oregon Health Science University Vaccine and Gene Therapy Institute, who led the research. "We are currently facing the annual flu season where seniors are at a particularly higher risk than the rest of the population. In fact, the majority of the 20,000 people who die each year because of the flu are over 65 years of age. We hope that years down the road, this research finding will help us boost the immune systems of the elderly, reducing this staggering number of deaths."

Nikolich-Zugich and colleagues uncovered this finding by working with a mouse model to study T-cells, specialized white blood cells that can fight off infection when a disease-causing pathogen is detected. Their research not only provides significant information about the workings of the body's immune system, it also points to the ways the body efficiently gets rid of pathogens and recovers from infection.

Specifically the researchers used mice infected with the herpes simplex virus to look at the quality of the T-cell response against the virus. They concentrated on molecules that sit on the surface of infected cells and alert T-cells. These molecules are part of the major histocompatability complex (MHC) system, a key component of the body's immune defense system.

"The MHC molecules have two roles. First, they act like the traffic cops in the body. They look for invaders and, once they find them, they call in T-cells to defeat a pathogen," explained Nikolich-Zugich. "But, just as importantly, they also 'train' T-cells when the pathogen is not around. They do this by selecting and expanding only those T-cells that can be appropriately directed to find and destroy a pathogen when it attacks."

"Up to this point, we did not know whether both of these roles were important in combating infection. What we determined was that the 'training' function, previously overlooked, was exquisitely important," he said.

By providing "training" to a wide, diverse set of T-cells, some MHC molecules can ensure that the pathogen will be met by the very best T-cells, able to kill the pathogen promptly at the beginning of infection. The findings showed that this can prevent pathogen-induced disease and death. Thus, the more diverse set of T-cells an animal has, the better chance the cells have of detecting a pathogen early and successfully fighting it off. The fact that as people age their T-cell diversity drops helps explain why seniors are more susceptible to the flu and other diseases than the rest of the population.

The research team chose to study herpes because it is a virus that rarely mutates and is easier for the body to spot than other viruses like HIV, which can mutate rapidly. However, by devising ways to achieve and maintain T-cell diversity, researchers hope to achieve better detection of other pathogens, including the rapidly mutating ones such as the AIDS-causing HIV, and fight them off before infection progresses to a higher level. Similarly, maintaining T-cell diversity during aging would go a long way towards reducing age-related illness and death due to infectious diseases.

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