Graft Versus Host Disease (GVHD) remains a significant issue in people receiving hematopoietic
cell transplants to treat various cancers, genetic immunodeficiencies and other diseases. In
GVHD, alloreactive T cells mediate this pathology, as T cell depleted hematopoietic transplants
to not induce GVHD. We have observed that following transplantation, donor CD8 T cells
undergo inflammasome activation, as measured by the activation of caspase-1. However, these
cells do not die via pyroptosis, which may alleviate their cytotoxic consequences in the host. We
also observe that these cells in which the inflammasome is activated hyperexpress a protein,
Ifi202, which is known to attenuate inflammasome activation, and human T cells similarly
express IFI16¿, which functions similarly in human cells. We hypothesize that Ifi202 limits the
degree of caspase-1 activation in these cells, and thus prevents these cells from undergoing
pyroptosis. The goal of this project is to determine the mechanism of inflammasome activation
in these T cells, and to determine the role of Ifi202 in preventing pyroptosis in CD8 T cells
during GVHD. We hypothesize that reduced Ifi202 expression in these cells will attenuate GVHD
pathology by increasing pyroptosis in alloreactive CD8 T cells.