title: Rapid thymic reconstitution following bone marrow transplantation in neonatal mice is VEGF-dependent.
abstract: Age-related differences in thymic function influence the rapidity of T cell reconstitution following hematopoietic stem cell transplantation (HSCT). In adults, thymic reconstitution is delayed until after marrow engraftment is established, and is significantly improved by approaches that increase marrow chimerism, such as pretransplantation irradiation. In contrast, we show that neonatal mice undergo more rapid and efficient thymic reconstitution than adults, even when bone marrow (BM) engraftment is minimal and in the absence of pretransplantation radiation. We have previously shown that the neonatal thymus produces high levels of vascular endothelial growth factor (VEGF) that drives angiogenesis locally. In this report, we show that inhibition of VEGF prior to HSCT prevents rapid thymic reconstitution in neonates, but has no effect on thymic reconstitution in adults. These data suggest that the early radiation-independent thymic reconstitution unique to the neonatal host is mediated through VEGF, and reveals a novel pathway that might be targeted to improve immune reconstitution post-HSCT.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Cuddihy
authors.forename: Batul T
authors.initials: BT
authors.lastname: Suterwala
authors.forename: Shundi
authors.initials: S
authors.lastname: Ge
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kohn
authors.forename: Julie
authors.initials: J
authors.lastname: Jang
authors.forename: Jacob
authors.initials: J
authors.lastname: Andrade
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Gay M
authors.initials: GM
authors.lastname: Crooks
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation; D006085:Graft Survival; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D060168:Thymocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D013950:Thymus Gland / Q000098:blood supply / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D018183:Transplantation Chimera; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology; D014916:Whole-Body Irradiation
chemical_list: D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor