[Impact of peri-SCT immune modulation on Treg homeostasis and GVHD]

Post allogeneic hematopoietic stem cell transplantation, CD4^＋CD25^＋Foxp3^＋ regulatory T cells (Tregs) play a central role in the maintenance of self-tolerance and immune homeostasis. In recent years, various immune-modulating agents, including cyclophosphamide, mogamulizumab, and antibodies to inhibitory co-stimulating molecules (CTLA-4 and PD-1), have been used to control donor-derived immunity or host-tumor burden during the peritransplant period; however, the underlying impact of these agents on Treg homeostasis is yet to be characterized. In particular, recent retrospective analyses suggested that blockade (an inhibitory molecule) before and after HSCT was associated with abnormal Treg homeostasis and the development of severe acute GVHD and other immune-mediated complications. Our recent studies, using murine model and clinical sample analyses, aim to define the effects of immune-modulating agents on the reconstitution of each lymphocyte subset, particularly in terms of Treg homeostasis. An enhanced understanding of the reconstituting mechanisms and the target-specificity of post-HSCT GVL response combined with novel immunotherapy will enable the development of a safe and efficient therapeutic strategy.