A study led by immunologist and Adult Bone Marrow Transplant Service Chief Marcel R. van den Brink has demonstrated a novel strategy for boosting numbers of infection-fighting T cells in mice after allogeneic bone marrow transplantation. The results, published in September in Nature Medicine, indicate the feasibility of using this approach to improve immune response in human transplant recipients. [PubMed Abstract]
Allogeneic bone marrow transplants require regimens of radiation and chemotherapy that wipe out the host immune system, leaving patients vulnerable to infection until their immune systems are reconstituted with donor cells.
To accelerate immune reconstitution, investigators cultured donor hematopoietic stem cells (HSCs), which make T cells, in mouse bone marrow engineered to express Delta-Like1 (DL1) -- a gene essential to T cell development. Mice receiving DL1-derived T cell precursors in addition to HSCs built a better defense against bacterial infection after transplantation than mice receiving HSCs alone. In mouse lymphoma models, adding DL1-derived cells to transplant tissue promoted graft-versus-tumor activity -- a beneficial phenomenon in which donor immune cells attack tumor cells. However, adding DL1-derived cells did not induce graft-versus-host disease, a potentially fatal complication of allogeneic transplantation.
"So far, this procedure seems to lead to numerous benefits without any obvious dangers," said Dr. van den Brink. He and his colleagues plan clinical trials.
