St. Jude study shows how T cell's machinery dials down au...( A St. Jude Childrens Research Hospit...),Health

A St. Jude Childrens Research Hospital study shows that T cells, the bodys master immune regulators, do not use simple on/off switches to govern the cellular machinery that regulates their development and function. Rather, they possess sophisticated molecular controls that enable them to adjust their function with exquisite precision. Such subtle adjustment enables T cells to modulate their development and function, including avoiding autoimmunity.

In autoimmune disease, rather than attacking invading microbes, the immune system attacks the bodys own organs, tissues or cells. Some 80 autoimmune diseases are known, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis and lupus.

Among the many mysteries surrounding autoimmune diseases is why they can sometimes take decades to manifest themselves, said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology. Our findings hint that this delayed onset could be explained by subtle defects in the molecular controls on T cells. Such T cells are white blood cells whose duties include shutting down the immune system when it has done its job and suppressing T cells that can attack the body.

Vignali is the senior author of a report on this work that appears in the advance online publication of the journal Nature Immunology.

The researchers explored the function of T cell receptors, proteins that span the cell membrane of T cells. These receptors receive outside signals that instruct T cells to develop, proliferate and transmit those signals into the cell. The St. Jude investigators sought to understand why T cell receptors need many copies of switch-like components called immunoreceptor tyrosine-based activation motifs (ITAMS). ITAMs are components of the CD3 adaptor proteins that attach to the T cell receptor and help transmit the control signals from the T cell receptor into the cell.

The ITAMs we studied are little molecular tags insi
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