VGTI researchers help uncover why aging reduces immune system function

December 02, 2004

PORTLAND, Ore. - Scientists at the Vaccine and Gene Therapy Institute at Oregon Health & Science University have made a discovery that helps explain why our immune system worsens with age. The work was led by Janko Nikolich-Zugich, M.D., Ph.D., a senior scientist at the VGTI. The scientists hope this new information can be used to better protect the elderly from infectious diseases by finding ways to slow or stop the degradation of the immune system. The research results are printed in the current edition of the Journal of Experimental Medicine.

"One of the major components of the immune system are T cells, a form of white blood cell. These cells are programmed to look for certain kinds of disease-causing pathogens, then destroy them and the cells infected by them," said Nikolich-Zugich who also serves as a professor of molecular microbiology and immunology in the OHSU School of Medicine, and is a senior scientist at the OHSU Oregon National Primate Research Center. "Throughout our lives, we have a very diverse population of T cells in our bodies. However, late in life this T cell population becomes less diverse, potentially resulting in a higher level of susceptibility to disease. We think we have found one of the key reasons behind this age-related susceptibility."

Specifically, in old age, the number of CD8 T cells diminishes. CD8 T cells have two functions: to recognize and destroy abnormal or infected cells, and to suppress the activity of other white blood cells to protect normal tissue. The scientists believe that late in life a different kind of CD8 T cell is increasingly produced by the body. These cells, called T cell clonal expansions (TCE), are less effective in fighting disease They also have the ability to accumulate quickly as they have a prolonged lifespan and can avoid normal elimination in the organism.

In the end, these TCE cells can grow to become more than 80 percent of the total CD8 population. The accumulation of this one type of cell takes away valuable space from other cells, resulting in an immune system that is less diverse and thus less capable in effectively locating and eliminating pathogens.

To conduct the research, scientists at the VGTI studied mice, which have immune system function very similar to humans. The scientists found the aging mice to have greater TCE levels than normal mice, a less diverse population of CD8 T cells and reduced ability to fight disease. In addition, the scientists were able to show that increasing TCE cells in a normal, healthy mouse reduces that animal's ability to fight disease.

"While this work is still in the early stages, we think it might be of great value," explained Nikolich-Zugich. "If we can find ways to limit the production of TCE in the aging, we might be able to keep their immune systems strong and better able to fight disease. To provide a real-life example: A flu vaccine shortage like the one we are witnessing might be less concerning if elderly Americans were made less susceptible."
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The research was supported by the National Institutes of Health, the DeWitt Wallace Fund, the OHSU Cancer Institute, the OHSU Department of Molecular Microbiology and Immunology and the OHSU Oregon National Primate Research Center.

Oregon Health & Science University

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