CD4+CD25+FOXP3+ Regulatory T Cells to Protect Against Graft Versus Host Disease

Allogeneic hematopoietic cell transplantation (HCT) has benefited many patients with hematological malignancies and bone marrow failure states. However, graft vs host disease (GVHD) and immune incompetence remain significant challenges that limit the field to the treatment of patients with life threatening, high-risk disorders due to the significant non-relapse mortality (NRM) associated with the treatment. With a greater understanding of the pathophysiology of GVHD it has become apparent that this disorder represents a dysregulated immune reaction resulting in immune dysfunction further exacerbated by the treatment with immunosuppressive medications and injury to lymphoid tissues where immune recovery and tolerance develop. The emergence of fundamental mechanisms of immune regulation, whose pioneers received the 2025 Nobel Prize in Physiology and Medicine, have resulted in new concepts for improving outcomes for patients and the hope that with reduction in transplant related risk HCT can be offered to more patients with a broader range of immune mediated disorders. In this review the history, preclinical studies and successful translation of CD4+CD25+FoxP3+ regulatory T cells (Treg) in the context of allogeneic HCT will be discussed.