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St. Jude investigators have developed a technique that significantly reduces the time and expense of studying how the body produces immune system cells called T lymphocytes that aggressively attack germs, cancer and other harmful targets.
The technique holds promise for accelerating studies of autoimmune diseases, which are caused when the body’s immune system attacks healthy cells, organs or tissues. For example, Type 1 diabetes is caused by T cells attacking insulin-producing cells in the pancreas.
The key to the new technique is its ability to quickly modify mice so they make large quantities of just one population of T lymphocytes, which has a specific type of T-cell receptor (TCR), according to Dario Vignali, PhD, Immunology. The TCR is a protein on the surface of T cells that binds to the specific target the cell is genetically programmed to attack. Variations in the TCR’s structure make each receptor unique and responsive to a different target. Vignali is senior author of a report on this work that appears in the March issue of Nature Methods.
The TCR is also critical to the thymus’ ability to identify and delete newly made T cells that cannot distinguish between the body and legitimate targets, such as bacteria. “Before we developed a way to quickly and efficiently produce mice with T cells that carried specific TCRs, much of the research in this area was too slow, especially for work that has such promise for developing new treatments for immune system diseases,” Vignali said. “Now we are working with these mice to study how T cells with the wrong TCR cause Type 1 diabetes.”
Jeff Holst, PhD, the postdoctoral scientist in Vignali’s laboratory who did much of the work, is first author of the Nature Methods paper. Other authors of this paper include Kate Vignali and Amanda Burton of Immunology.
Last update: March 2006