Graft versus Host Disease
GVHD in Bone Marrow Transplantation
Allogeneic hematopoietic stem cell transplantation (HSCT) is used for treatment of several hematological malignancies as well as immune disorders. For successful outcome, a large number of donor T cells are infused along with hematopoietic stem cells.
HSCT without T cells results in poor engraftment and recurrent infections. Infused T cells also mediate anticancer effect against some lymphoma and leukemia. However, these donor T cells recognize the recipient’s cells as foreign and attack the epithelial cells in the skin, liver and gut causing acute graft versus host disease (GVHD) that accounts for significant morbidity and about 50% mortality associated with HSCT. Therefore, it is essential to identify the molecule(s) in donor T cells that are responsible for induction of GVHD.
I have been studying the cellular mechanism of GVHD and the interactions between subpopulations of T cells involved in induction or prevention of the disease. My research demonstrates that naive phenotype subset of T cells (memory phenotype) that cause acute GVHD while memory phenotype T cells do not. Memory phenotype T cells have these unique characteristics i) reduced proliferation and IL-2 production in response to recipient antigens (allo-antigens) and ii) have reduced ability to traffic to target to GVHD target organs. Therefore, I intend to identify transcription factors and cell signaling molecules that regulate their functions.
Pathophysiology of Graft versus Host Disease
Publications
Journal of Immunology 2007 179(10) 6547