Allogenic hematopoietic stem cell transplantation (HSCT) is a procedure that infuses a donor’s healthy blood-forming stem cells into a recipient as part of a potentially curative therapy for cancer. While this therapy can be life-saving, a major complication is the development of graft-versus-host disease (GVHD), which causes significant morbidity and can be fatal. Before allogenic HSCT, a patient receives a conditioning regimen, chemotherapy designed to deplete his/her normal white blood cells, including T cells. But a new study by investigators from Brigham and Women’s Hospital, University of Oslo (Norway) and University of Newcastle (UK) has found that skin and intestinal T cells in the recipient survive conditioning regimens and continue to perform their normal functions. But, under certain conditions, these T cells can become activated by donor white blood cells and play a previously unappreciated role in acute GVHD. The investigators’ results are published in The Journal of Clinical Investigation.