The immunopathology of thymic GVHD

The clinical success of allogeneic hematopoietic stem cell transplantation (HSCT) depends on the appropriate reconstitution of the host’s immune system. While recovery of T-cell immunity may occur in transplant recipients via both thymus-dependent and thymus-independent pathways, the regeneration of a population of phenotypically naive T cells with a broad receptor repertoire relies entirely on the de novo generation of T-cells in the thymus. Preclinical models and clinical studies of allogeneic HSCT have identified the thymus as a target of graft-versus-host disease (GVHD), thus limiting T-cell regeneration. The present review focuses on recent insight into how GVHD affects thymic structure and function and how this knowledge may aid in the design of new strategies to improve T-cell reconstitution following allogeneic HSCT.