My laboratory studies T lymphocyte function and development in hematopoietic stem cell transplantation (HSCT). T cells have multiple important roles in determining clinical outcomes in HSCT. Donor T cells transferred with the hematopoietic stem cells are required for anti-tumor immunity to prevent relapse of malignant disease as well as for mediating protective immunity against infection. However, donor T cells are capable of generating robust immune responses to recipient alloantigens which causes graft versus host disease (GVHD), a multi-organ inflammatory condition that is a significant cause of morbidity and mortality. We are interested in understanding the molecular events that define the recognition of alloantigens by T cells, and how that results in T cell activation and generation of effector mechanisms ultimately responsible for GVHD. We utilize transgenic animal models, human T cell culture systems, gene expression analyses, and flow cytometry to examine T cells from patients with GVHD in an attempt to define the mechanisms driving disease.
A related area of study in the laboratory is the examination of T cell development after HSCT. While donor-derived T cells are important contributors to protective immunity after HSCT, de novo development of T cells in the recipient thymus is essential for establishing maximally effective immunity to pathogens as well as preventing the development of autoimmune diseases in the post-transplant setting. T cell development occurs in the thymus, which has stromal components specialized to support T cell development. Thymic function is compromised in HSCT patients, owing to toxicity of pre-transplant regimens, GVHD affecting the thymic stroma, and age-related thymic degeneration. We are investigating how these stimuli affect T cell development in the thymus and subsequent immune system function.