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Penn study demonstrates new way to boost immune memory
Date:6/4/2009

my of so-called effector cells that can clear infection. However, TRAF6-deficient CD8 T cells do not develop into a population of memory cells that can recall a particular infectious agent when the body encounters it a second time.

Using microarray analysis and a program that searches protein pathways, the team compared the gene expression profiles of TRAF6-deficient cells and cells with TRAF6 to see what stood out. "We discovered differences in genes that regulate fatty acid metabolism," says Pearce. Fatty acids can be broken down for energy and the microarray analyses revealed that TRAF6-deficient CD8 T cells exhibit altered expression of genes that regulate this process.

Consistent with the microarray findings, CD8 T cells lacking TRAF6 display defective fatty acid oxidation in response to growth factor withdrawal. Giving the mutant mice the metformin restored fatty acid oxidation and the generation of memory cells that lack TRAF6. Remarkably, this treatment also increased the generation of memory cells in normal mice, and consequently was able to significantly improve the efficacy of an experimental anti-cancer vaccine. A lack of fatty acid metabolism is correlated with lack of T-cell memory and through in vitro studies the team also saw that T cells burn more fatty acids when given metformin.

T cells proliferating to form an army of effector cells burn glucose for their energy. Non-proliferating T cells, such as memory cells, burn fatty acids, amino acids, and glucose interchangeably in a different metabolic pathway. From this, explains Pearce, "it is implied that there's a switch in metabolism somewhere along the way between proliferating and non-proliferating T cell populations." Perhaps at the peak of the proliferation, when energy is limiting and cells are metabolically stressed, there is a switch to another energy pathway to survive, say from glucose to fatty acids.

"Most T cell vaccines have a good initial resp
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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