Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for patients with a variety of hematologic malignancies, such as leukemia, lymphoma, and for some solid tumors. However, the post-transplant immunosuppression associated with the conditioning regimens limits its wider application. Delayed immune reconstitution, especially in the CD4 T cell lineage, is associated with an increased risk of opportunistic infections and malignant relapses, and is widely recognized as one of the most important clinical hurdles for allo-HCT. The primary focus of the research team of Dr. Enrico Velardi at the Bambino Gesù Children's Hospital (Rome) is to understand the mechanisms driving immune reconstitution after insults, with a particular emphasis on the process of thymic regeneration, in order to identify novel therapies to enhance T-cell immunity. Such interventions could be valuable, not only for recipients of HCT, but also for individuals with T cell deficiencies due to aging (immunosenescence), infectious diseases, radio- or chemo-therapy. In this talk, Dr. Velardi will discuss his recent work in this field.