Abstract
Abstract 4485Myeloablative conditioning prior to bone marrow transplantation (BMT) results in thymic epithelial cell (TEC) injury, T cell immune deficiency, and susceptibility to opportunistic infections. Conditioning regimen-induced TEC damage directly contributes to slow thymopoietic recovery following BMT. Keratinocyte growth factor (KGF) is a TEC mitogen that stimulates proliferation and, when given prior to conditioning, reduces TEC injury. Some TEC subsets are refractory to KGF and functional T-cell responses are not fully restored in KGF-treated BMT recipients. Therefore, we investigated whether the addition of a pharmacological inhibitor, PFT-β to transiently inhibit p53 during radiotherapy could spare TEC from radiation-induced damage in congenic and allogeneic BMT. The combined pre-BMT administration of KGF plus PFT-β additively restored numbers of cortical and medullary TEC and improved thymic function post-BMT, resulting in higher numbers of donor-derived, naïve peripheral CD4+ and CD8+ T-cells. Improved T-cell reconstitution correlated with enhanced recovery of fibroblastic reticular cells in the lymph node stromal compartment, and a superior immune response against L. monocytogenes infection. Thus, transient p53-inhibition combined with KGF represents a novel and potentially translatable approach to promote rapid and durable thymic and peripheral T-cell recovery following BMT. Disclosures:No relevant conflicts of interest to declare.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have