Ait-Oufella et al., Nature Medicine, 5 February 2006 [e-pub ahead of print].

Heart Trouble.
Mice with healthy regulatory T cells have smaller atherosclerotic lesions (left) than do those without them.

T Cells to the Rescue

Who knew that a T cell could be so versatile? One kind of these immune cells, already thought to ease autoimmune disease and organ transplant rejection (ScienceNOW, 22 July 2004,), now appears to prevent atherosclerosis in mice. The work, although preliminary, may begin to explain how the immune system influences the potentially deadly disease.

An enduring mystery of atherosclerosis--the blockage of arteries that can lead to heart attack and stroke--is why T cells flock to atherosclerotic lesions, sites of inflammation lining blood vessels. For decades, scientists have wondered whether those cells are aggravating the disease or somehow countering it. Because regulatory T cells reduce inflammation in lab animals, cardiologist Ziad Mallat at the French National Institute of Health in Paris and his colleagues theorized that regulatory T cells are trying to protect against atherosclerosis.

The team tested the idea by irradiating mice to eliminate their T cells. Some of the animals received normal T cells back, and others got cells deficient in a surface molecule that activates regulatory T cells. All the mice were fed a high-fat diet for 20 weeks. Those without the surface molecule developed much more severe lesions, and higher numbers of them.

To ensure that a lack of regulatory T cells was the culprit, Mallat and his colleagues turned to a different set of mice that were devoid of T cells and genetically susceptible to atherosclerosis. Those given mature regulatory T cells didn't develop the disease. But mice that received regulatory T cells that were unable to activate and function properly suffered severe atherosclerotic lesions, the group reports in the 5 February online Nature Medicine.

The work "implicates this regulatory T cell as being involved in atherosclerosis," says Alan Daugherty, head of the cardiovascular research center at the University of Kentucky in Lexington. Still, he says, other groups have arrived at opposing results regarding the role of T cells in the disease, in part, perhaps, because their animal models aren't the same. Mallat hopes to clarify the role of regulatory T cells with a new experiment: injecting the cells into genetically normal mice with atherosclerosis, to see whether the cells can treat the disease.

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