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St. Jude Study Shows How T Cell's Machinery Dials Down Autoimmunity
Date:5/12/2008

al ITAMs crippled a process called "negative selection." In this process, the immune system rids itself of immature T cells that might attack the body's own cells, causing autoimmune disease. Vignali said that these findings might provide insight into how autoimmune diseases start.

"One implication of our findings is that a relatively small defect in the efficiency of signal transduction through the T cell receptor could give rise to a subtle failing in negative selection, which gives rise over a long period of time to a few overly active T cells that might initiate autoimmunity," Vignali said. "Clearly from our studies there is the possibility that you don't really need a very big reduction in T cell receptor signal strength to have a defect in negative selection."

The study also showed that different T cell functions required different numbers of functional ITAMs. "We were surprised to find that many ITAMs were required to make T cells divide and expand, but only one or two was required to make T cells secrete cytokines," Vignali said. Cytokines are soluble proteins used by cells of the immune system to communicate and send messages to one another. Vignali said these basic findings represent only the beginning of more detailed studies of the role of ITAMs in T cell function.

"We believe this idea that T cell signaling acts more like a rheostat than an on/off switch offers significant new insights into how T cell development and function is controlled," Vignali said.

Other authors include Haopeng Wang, Kelly Durick Eder, Creg Workman, Kelli Boyd, Zachary Baquet, Karen Forbes and Richard Smeyne (St. Jude); Harvir Singh, Andrzej Chruscinski and Paul Utz (Stanford University School of Medicine, Stanford, Calif.); and Nicolai van Oers (The University of Texas Southwestern Medical Center, Dallas).

This work was supported by the National Institutes of Health, a Cancer Center Support CORE grant and ALSAC.

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SOURCE St. Jude Children's Research Hospital
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