α-MyHC is unfamiliar to T Cells since it is not produced in the thymus where T cells are primed to recognize harmful molecules.
Inflammations of the heart muscle are caused because T cells attack α-MyHC, a type of heart muscle protein called, according to researchers at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and colleagues in the U.S.
The paper “Impaired thymic tolerance to α-myosin directs autoimmunity to the heart in mice and humans” was published March 23 in the Journal of Clinical Investigation.
After studying mice that are often spontaneously affected by fatal myocarditis, the researchers discovered that the target of the T cells was α-MyHC. This protein is highly specific to the heart muscle and not found in muscles of the skeleton.
Professor Bruno Kyewski of DKFZ hypothesized that the T cells attack α-MyHC because the heart protein is not within the thymus tissue of the mice. As a result, α-MyHC is unfamiliar to the T cells during their early development in the thymus gland, where they come to recognize and tolerate many of the body’s molecules.
To test that hypothesis the researchers modified the mice’s genetic material so that their thymus gland became capable of producing α-MyHC. These animals were no longer affected by autoimmune myocarditis. And since the human thymus does not produce α-MyHC, either, the hypothesis appears to be valid for humans as well.
While human T cells permanently circulate in the bloodstream with the potential of attacking the heart, it is normally not a problem. “But if the cardiac muscle gets damaged by a viral infection or an infarction and larger amounts of α-MyHC are released from the defective tissue, the fragile tolerance breaks down,” says Kyewski.
The research is expected to help in development of T-cell specific treatments against autoimmune myocarditis, which often precedes a dangerous and often fatal heart enlargement. While a common approach has been to attempt to suppress the production of antibodies in patients, “now we know that we have to selectively block specific T cells to protect the heart in such cases,” Kyewski adds.