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Molecular Requirements for the Development of Intestinal T Cells

Podd, Bradley Stephen
Thesis/Dissertation; Online
Podd, Bradley Stephen
Bender, Timothy
Tung, Ken
Camerini, Victoria
Braciale, Thomas
Roberts, Margo
Ley, Klaus
Kutchai, Howard
Mucosal surfaces are enriched for unconventional T cells. The largest population of unconventional T cells is intestinal intraepithelial lymphocytes (IEL), which are comprised of cells expressing a unique CD8 homodimers with either the TCR  or TCR  antigen receptors. Unconventional T cells are intricately intertwined with epithelial barrier homeostasis through the production of growth factors and the elimination of damaged, infected or transformed epithelial cells. The fast kinetics of unconventional T cell responses, combined with a limited diversity of antigenic determinants has placed these cells at the boundaries of the innate and adaptive immune systems. Moreover, atypical T cell populations have potent regulatory function towards other T cell populations. The origin of these cells, as well as the molecular requirements for their development and maintenance are poorly understood. Here, we provide evidence that clarifies the molecular requirements for the development of these cells. First, we take advantage of a  TCR transgenic system to define the antigenic requirements for the development of CD8+ IEL. Second, we defined the MHC IIdependence of a subset of TCR + si-IEL expressing the V7 chain. Third, we determined that V7+ T cells residing within organized lymphoid aggregates in the gut wall are clonally related to a subset of V7+ si-IEL. These data provide new insight to three related issues in the development and maintenance of unconventional T cell populations. Alterations in unconventional intestinal T cell homeostasis have broad implications in autoimmune and inflammatory disease. Note: Abstract extracted from PDF text
University of Virginia, Department of Molecular Physiology and Biological Physics, PHD, 2008
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