REGULATORY T CELL HETEROGENEITY IN THE RESOLUTION OF ACUTE LUNG INJURY

Regulatory T cells (Tregs) are critical to maintain immune homeostasis, prevent undue immune activation during inflammatory responses, and to facilitate repair of damaged tissue. Limitations in Treg numbers in experimental mouse models, as well as challenges in primary Treg culture and expansion, have limited in vitro studies of Treg phenotypes. Chapter 1 of this dissertation explores a novel potential tool with which to probe aspects of Treg function, MT-2 cells, which are an immortalized human Treg-like cell line. We found that genetic manipulation of MT-2 cells are possible, and that several key aspects of suppressive Treg function and gene expression are impaired when the Treg lineage-defining transcription factor FOXP3 is deleted.Chapter 2 of this dissertation addresses a key question regarding Treg contributions to the resolution of acute lung injury. The use of in vivo mouse models lacking the ability to induce the Treg fate in naïve and effector CD4+ T cells in the periphery reveals non-redundant roles for peripheral Tregs in the establishment of the lung immune landscape, as well as during the response to a murine H1N1 influenza infection. The results of these studies advance the field of Treg biology and offer insights into the development of Treg cell therapies, which show significant promise in facilitating immune suppression in several disease states.