The study of cellular deletion is essential to understanding the body's immune system Lauren Harte Mentor: Patrick Stuart, Ph. D Department of Ophthalmology, and Department of Molecular Microbiology Washington University School of Medicine Saint Louis, MO The study of cellular deletion is essential to understanding the body's immune system. After an infection, the body must delete all of its excess T-cells and needs only memory cells to recognize the antigen again. If deletion does not occur after a toxin, bacteria, or any such foreign entity enters the body other problems may surface. One such problem is autoimmunity. For instance, those undeleted T-cells that are generated towards foreign entities that share antigenic epitopes with self can cause direct harm to the body. Harm may also be caused in the form of autoimmunity when T-cells that are no longer needed attack the body's own cells and organs. By knowing exactly how the body executes apoptosis (cell mediated death), and destroys these T-cells, such problems can be better understood and combated. Fas-Ligand, a molecule that controls homeostasis and the deletion of T-cells in the body is the focal point in our study of apoptosis. Fas-Ligand works in conjunction with several different cytokines that affect deletion efficiency in the body. The experiment that I worked on focused on the role of the cytokine Interleukin-10 (IL-10), in superantigen Staphylococcal Endotoxin B (SEB)-deletion. SEB induces 20% to 30% of all T-cells in our mouse models, which makes its effects easier to detect. When SEB enters the body, an antigen-presenting cell presents it to a T-cell receptor, thereby activating those T-cells to proliferate. Following activation, the T-cells are no longer engaging their T-cell receptors and are now susceptible to Activation Induced Cell Death by Fas-Ligand. Fas-Ligand, which is expressed by several different cell types, initiates a cascade of various molecules and cytokines that destroy the excess T-cells. We wished to determine whether the cytokine IL-10 up-regulates or down-regulates cellular deletion. We hypothesized that it would up-regulate Fas-Ligand, allowing for more efficient apoptosis. The effects of IL-10 could be studied by measuring T-cell counts after an injection of SEB into C57BL/6 mice that can produce IL-10, or IL-10 Knockout (IL-10 KO) mice that cannot. The mice were injected with SEB, causing T-cell activation. The Vb8 T-cells (about 20% of mouse T-cells express Vb8) that were activated by SEB were measured on days 0, 3, 6, 12, and 28 by bleeding the mice. We expected that SEB deletion would not be as great in mice lacking IL-10 because of our hypothesis. The results show that C57BL/6 mice experienced more efficient SEB deletion than the IL-10 KO mice. We believe that this difference is due to the ability of IL-10 to up-regulate Fas-Ligand expression, thereby allowing for faster deletion of Vb8 T-cells. Studies are planned to test this hypothesis. In addition, in the future we plan to assess the role of cytokines such as Tumor Necrosis Factor-a, and Interleukin-4 in SEB-induced deletion. Research in this area will place us one step closer to understanding the intricacies involved in the cell-death pathway associated with Fas/Fas-Ligand. And perhaps one day, as a result of the work completed in Dr. Stuart's laboratory, we will have better tools to deal with diseases such as autoimmunity Scholar Index Next   Natural Sciences Learning Center Washington University - Biology All contents copyright © 2001 Email comments to nslc webmanager