RUI: The origin and function of mature Nur77low T cell subpopulations in the thymus

Haverford College, Haverford PA

Investigators

Abstract

T lymphocytes, a group of white blood cells, continually scan our tissues for evidence of infection. They can recognize cells that have been infected and initiate powerful immune responses against these cells as well as against the pathogen responsible for infection. Immature T lymphocytes (also known as thymocytes) have to be "trained" to distinguish uninfected from infected cells. This research team has developed an elaborate system to select young T lymphocytes that have potential to make this distinction from among the millions that are generated daily. This selection process occurs in a specialized organ called the thymus and is a critical step in keeping us safe from autoimmune reactions. In order to mature successfully, thymocytes must interact extensively with specialized cells known as thymic epithelial cells. These interactions determine which immature T cells can safely enter circulation. This project examines the interesting possibility that mature T lymphocytes, themselves, play a role in shaping these all-important interactions. Using genetically modified mouse strains and a set of imaging tools that can be used to identify and trace cells in the thymus, these investigators will test an original hypothesis that a special group of fully mature T lymphocytes stay in the thymus and enhance the ability of epithelial cells to select the most useful and least dangerous immature T lymphocytes for further maturation. By improving our understanding of the molecular and cellular participants in T cell selection, these studies will shed light on what can go awry and contribute to autoimmune disease. This investigation will also contribute directly and significantly to the training of young scientists. The studies described will be performed exclusively by undergraduates, who were also the inspiration for the project. The investigator has a very strong track record of educating young scientists: 95% of the seventy-five senior undergraduates mentored in her lab over the last sixteen years have pursued post-graduate studies in medicine, research, education, and public health.