title: Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children.
abstract: Thymus-dependent T-cell regeneration is a major pathway for immune reconstitution after stem cell transplantation in children. Therefore, we prospectively assessed T-cell dynamics and thymic function in 164 pediatric patients between 1 and 124 months after transplantation by measuring T-cell receptor recombination excision circles and spontaneous expression of Ki67 in peripheral T-cell subsets. We analyzed the effect of recipient age, conditioning regimen, type of donor and graft, stem cell dose, and graft-versus-host disease on the onset and the plateau of thymic output. A high rate of spontaneous proliferation in early-reconstituting naive and memory T cells inversely correlated with total T-cell numbers. Accordingly, T-cell receptor recombination excision circle content was diminished in early-appearing naive T cells. A multivariate analysis revealed that the onset of thymic recovery was inversely correlated only with recipient age ( P < .0002), whereas the plateau of thymic output was higher in patients receiving increased stem cell numbers ( P < .0022). Donor type, stem cell source, and conditioning regimen influenced none of the analyzed parameters. In conclusion, lymphopenia-driven proliferation is important for T-cell homeostasis in children early after stem cell transplantation, but it might result in underestimation of thymic function. Onset and plateau of thymic activity are independently regulated by different transplant-related factors.
authors.affiliation: Children's Hospital, Pediatric Stem Cell Transplant Program, University of Tübingen, Germany. Eyrich_M@klinik.uni-wuerzburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Eyrich
authors.forename: Gernot
authors.initials: G
authors.lastname: Wollny
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Tzaribaschev
authors.forename: Klaus
authors.initials: K
authors.lastname: Dietz
authors.forename: Dorothee
authors.initials: D
authors.lastname: Brügger
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Karin
authors.initials: K
authors.lastname: Schilbach
authors.forename: Beate
authors.initials: B
authors.lastname: Winkler
authors.forename: Dietrich
authors.initials: D
authors.lastname: Niethammer
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schlegel
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015329:Gene Rearrangement, T-Lymphocyte; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000032:analysis; D008231:Lymphopenia; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods
chemical_list: D019394:Ki-67 Antigen; D019653:Myeloablative Agonists