Trudeau discoveries add to knowledge of aging immunity, platelet disorders
SARANAC LAKE – Trudeau Institute has announced two new research findings from its scientists that could have implications for the elderly and for people suffering from platelet disorders.
The news was issued Tuesday in a pair of press releases from the nonprofit, Saranac Lake-based biomedical research center.
Immunity and aging
Researchers from Trudeau have recently uncovered abnormal behavior in aging cells that helps explain the loss of previously acquired immunity. The findings were made available Monday on the website of the online scientific journal Immunity & Aging. The paper was authored by Lisa M. Connor, Jacob E. Kohlmeier, Lynn Ryan, Alan D. Roberts, Tres Cookenham, Adam A. Quinn, Marcia A. Blackman and David L. Woodland.
The research team focused on “memory” T-cells, a type of white blood cell that fights infection and tumor development. Memory T-cells created after an infection have the capacity to “remember” the prior pathogen; upon secondary exposure, they typically respond with accelerated speed and strength.
A key question for researchers is how these memory T-cells can be maintained into old age. The memory pool becomes progressively dysregulated with age, such that large expansions of identical cells (or clones) occur in the elderly. These clonal expansions are found in most individuals and are thought to contribute to age-associated immune dysfunction. Understanding how and when these clonal expansions develop is a key focus of aging research.
The Trudeau team developed, in a mouse model, a way to track the early development of these clonal expansions and test their impact on the ability of the mice to respond to reinfection. Their data show that the clonal composition of the virus-specific memory CD8+ T cell pool begins to change within months of the initial infection. These early clonal perturbations eventually result in large clonal expansions that have been associated with aging.
Importantly, most of these expanded clones are significantly impaired in their capacity to mount recall responses to secondary challenge in vivo. However, as reinfection promotes the expansion of the normal memory cells in the pool, this raises the possibility that booster vaccination regimes could overcome the increasingly dysregulated immune response in the elderly.
The new information should be helpful to immunologists working to develop improved vaccine protocols for elderly populations.
An international contingent of immunologists, led by Trudeau faculty member Marcia A. Blackman, has established an experimental mouse model that will allow researchers to answer fundamental questions about the biological origins of thrombocytopenia, a decrease in platelet levels which can lead to excessive bleeding, caused by gammaherpesviruses like Epstein-Barr virus. The new mouse model will allow researchers to test therapeutic strategies that may have implications for the treatment of human forms of the disease, which can prove fatal.
The research currently appears online at www.sciencedirect.com and will appear in print in the Journal of Autoimmunity.