Ghrelin Protects the Thymic Epithelium From Conditioning-Regimen-Induced Damage and Promotes the Restoration of CD4+ T Cells in Mice After Bone Marrow Transplantation.

Abstract

The delay in immune reconstitution after hematopoietic stem cell transplantation (HSCT), especially a delay in central immune reconstitution, leads to opportunistic infections and disease relapse after transplantation and affects the long-term outcome of HSCT. This delay is mainly attributable to thymic damage after myeloablative chemotherapy and radiotherapy. We established a model of allogeneic bone marrow transplantation (BMT) in mice and administered ghrelin (GRL) 7 days before the conditioning regimen or the day after BMT to explore the effect of GRL on thymus. All the GRL-treated mice, especially those administered GRL before the conditioning regimen, exhibited more intact thymic architecture and a more rapid restoration of CD4 T lymphocytes after BMT than those of the corresponding control mice. Moreover, the levels of T cell receptor excision circles were significantly higher in the mice treated with GRL before the conditioning regimen than in the control mice at 28 days after BMT. Our findings suggest that GRL may be a novel potential therapeutic approach to protecting the thymic epithelium from conditioning regimen-induced damage and promoting rapid and durable thymic and peripheral CD4 T cell recovery after HSCT.