New Research Helps Explain Weakened Immune Response in Elderly

Trudeau Institute Investigators Use Mouse Models to Examine Loss of Natural Cell Immunity in Aging Cells and Potential Vaccine Improvements

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MARCIA A. BLACKMAN, PH.D.

Saranac Lake, New York (PRWEB) January 08, 2013

Researchers from the Trudeau Institute have recently uncovered abnormal behavior in aging cells that helps explain the loss of previously acquired immunity. The findings were made available yesterday on the website of the online scientific journal Immunity & Ageing.

The paper, titled “Early dysregulation of the memory CD8+ T cell repertoire leads to compromised immune responses to secondary viral infection in the aged,” 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 new information should be helpful to immunologists working to develop improved vaccine protocols for elderly populations.

The research team focused on “memory” T-cells, a type of white blood cell that fights infection and tumor development. Memory T-cells generated following 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. It is well known that 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 sensitive new assay that allowed them to track the early development of these clonal expansions and test their impact on the ability of the mice to respond to re-infection. 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 re-infection 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.

These data illustrate how experiments in mouse models can reveal fundamental principles that can be applied to human medicine. The abstract for the paper can be accessed at http://www.immunityageing.com/content/9/1/28/abstract.

About the Trudeau Institute
The Trudeau Institute is a nonprofit biomedical research center founded in 1884 by Dr. E.L. Trudeau. The Institute's fundamental research on immunity fosters the development of vaccines, treatments and cures for many life-threatening diseases, including cancer, tuberculosis and influenza. The Institute is supported by federal and state grants and contributions from individuals, private foundations and corporations. For further information about the Trudeau Institute, go to http://www.trudeauinstitute.org.
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