Connections between starvation and immunological memory

Researchers at Emory have been revealing several connections between cells’ responses to starvation and immunological memory. The latest example of this is a paper in Nature Immunology from Rafi Ahmed’s lab, showing that the cellular process of autophagy (literally: self-consumption) is essential for forming and maintaining memory T cells.

This finding has some practical implications for vaccination and could point the way to additives that could boost vaccine effectiveness in elderly humans. Researchers at Oxford have demonstrated that autophagy is diminished in T cells from aged mice, and T cell responses could be boosted in older mice using the autophagy-inducing compound spermidine.

GCN2 autophagy

Autophagy here is indicated by green speckles, while red indicates vaccine antigens. Thanks to Pulendran lab for image.

In the Nature Immunology paper, Ahmed’s team showed (using its workhorse LCMV infection model) that autophagy is activated as T cells make the transition to memory and if genes needed for autophagy are disrupted in mice, so is memory T cell formation. The first author is The researchers hypothesize that autophagy is helping to preserve T cells that have recently undergone a burst of proliferation, by performing functions such as removal of misfolded proteins or damaged mitochondria that generate reactive oxygen species.

Some previous evidence for the autophagy-immunity connection has come with Bali Pulendran’s lab’s study of the yellow fever vaccine and the autophagy-regulating gene GCN2. It also weaves together with the Ahmed’s lab previous discovery that the drug rapamycin, usually thought of as an immunosuppressant, can promote memory cell formation.

The Ahmed lab’s results contradicted some previous reports on autophagy in T cells, which had found that autophagy was important for the initial burst of T cell expansion. Ahmed’s team used a strain of mice engineered to delete autophagy-related genes only after T cell activation, so that the T cells would be normal at the time of viral infection. Previous studies used mice that deleted autophagy-related genes during T cell development, which means that the T cells were abnormal for a long time before being called upon to proliferate.

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Posted on by Quinn Eastman in Immunology Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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