Autoimmune Disease Triggered If T Cells Miss A Single Protein Early On

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Scientists have discovered that autoimmunity can be triggered in the thymus, where the immune system's T cells develop, if T cells fail to recognize just one of the body's thousands of proteins as "self." The research confirms an emerging view that autoimmunity can start in this cradle of the immune system, and not only at the sites where autoimmune diseases emerge, such as the pancreas in the case of type 1 diabetes, or the joints in rheumatoid arthritis.

The discovery, from a mouse model of a human autoimmune condition, suggests that effective strategies to treat autoimmune disease should target not only the "peripheral" sites where autoimmune disease is active, but also the thymus - the organ where T cells and self-proteins, or self-antigens, first interact.

The research was led by investigators at the University of California, San Francisco (UCSF). It was published online November 20 by the Journal of Experimental Medicine and will appear in the journal's print edition November 27.

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T cell soldiers encounter the body's full array of proteins in the thymus, and those T cells with receptors that recognize "self" proteins, or antigens, normally are purged to avoid autoimmune attacks in the body later on. The new research showed that if just one of the body's antigens is not recognized as "self," this single failure can lead to a severe autoimmune disease in the retina.

"The thymus is like a filter," said Mark Anderson, MD, PhD, assistant professor of medicine at the UCSF Diabetes Center, and senior author of a scientific paper describing the discovery. "It is removing or pulling out autoreactive T cells. What this new study shows is if just one self-antigen is missing as the T cells go through the filter, it looks like this alone can lead to an autoimmune disease."

"The finding supports the promise of treatments targeting individual body proteins or antigens since we have shown that a single self-antigen can trigger disease," he added.

A similar mechanism may be at play involving other autoimmune diseases such as type 1 diabetes, Anderson said. Immunologists have demonstrated that insulin is expressed in the thymus

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