Scientists have made great strides in understanding how the thymus functions, including the timing, regulation, and mechanism of the process of negative selection, according to an article released on August 4, 2008 in the open-access journal PLoS Biology.

The immune system has a highly evolved method of preparing its cells to attack foreign materials (“non-self”) while allowing cells from the body (“self) to live undisturbed. This concept, sometimes known as central tolerance, is arranged during the development of immune T-cells in the thymus, an organ found in the chest in a process called negative selection. When the immune cells are created, they are subjected to a filtration process, in which only immature cells that are set to attack foreign material are allowed into the system. The mechanics of this process have not yet been well characterized, including its timing and regulation. In particular, the regions of the thymus known as the medulla and cortex could have different functions, including negative selection.

To investigate how the thymus performs this process, Sejin Ahn and colleagues, in a collaboration across the U.S., Korea, and the U.K., used genetically engineered mice with a specific protein called LacZ expressing only in cells of the cortex of the thymus. Upon analysis of the T-cells in the mature mice, all immune cells that might attack this LacZ protein were not present. This implies that the proteins present in the cells of the cortex are related to the types of proteins recognized by T-cells. This means that the cortex of the thymus plays a role in negative selection, helping make the T-cells tolerent to the body’s cells.

According to the researchers, this process is quite effective, “such that a relatively tiny number of antigen molecules present in a small fraction of the cells in the thymic cortex can singularly perform proofreading of all developing thymocytes.” Through this research, important information can be gleaned regarding the internal mechanics of the thymus as well as negative selection.

About PLoS Biology

PLoS Biology is an open-access, peer-reviewed general biology journal published by the Public Library of Science (PLoS), a nonprofit organization of scientists and physicians committed to making the world’s scientific and medical literature a public resource. New articles are published online weekly; issues are published monthly. For more information, visit http://www.plosbiology.org

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world’s scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org

TSCOTþ thymic epithelial cell-mediated sensitive CD4 tolerance by direct presentation.
Ahn S, Lee G, Yang SJ, Lee D, Lee S, et al.
PLoS Biol 6(8): e191.
doi:10.1371/journal.pbio.0060191
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Written by Anna Sophia McKenney