Dr. Xuefang Cao's lab studies immune reconstitution after hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT is a potentially curative treatment for leukemia, lymphoma, other hematologic and non-hematologic malignancies and non-malignant diseases. Lymphocyte reconstitution after HSCT is vital process that impacts clinical outcomes through affecting infection immunity, tumor immunity and donor-host tolerance. There are two pathways for T lymphocyte reconstitution: 1) thymus-independent pathway whereby pre-formed T cells (passenger) contained in the infused hematopoietic cells result in adoptive transfer of competent donor-derived T cells; 2) thymus-dependent pathway whereby hematopoietic stem cells or lymphoid progenitors undergo de novo regeneration of donor-derived T cells. Achieving balanced immune reconstitution is critical for patients' prognosis and their long-term quality of life. However, graft versus host disease (GVHD) remains a major obstacle for allogeneic HSCT. GVHD is mediated by donor-derived T cells which recognize genetically distinct host as non-self, subsequently leading to host cell destruction. On the other hand, donor-derived T cells can protect the patients from infection, and can also identify and attack host tumor cells, producing the beneficial graft-versus-tumor (GVT) effect. Current strategies for GVHD prevention and treatment are universally immunosuppressive. Unfortunately, such strategies are not always successful, and may adversely affect immune reconstitution leading to infection or reduced GVT effect that may result in cancer relapse or secondary malignancy. Preferably, therapeutic interventions could be developed to prevent GVHD through selective inhibition of pathogenic T cells, while balancing a reconstituted immune system that is capable of maintaining tumor immunosurveillance and infection immunity. To this end, my lab focuses on investigating the cellular and molecular mechanisms governing T cell differentiation, activation and effector function after allogeneic HSCT. Specifically, we are currently studying HSCT patients and murine models in order to define the roles of co-stimulation pathways and cytotoxic molecules in T cell reconstitution and T cell-mediated GVHD and GVT effect. The goal of our work is to exploit these pathways to develop novel strategies that can improve immune reconstitution to benefit HSCT patients.