Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children

Biol Blood Marrow Transplant. 2005 Mar;11(3):194-205. doi: 10.1016/j.bbmt.2004.12.001.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cohort Studies
  • Gene Rearrangement, T-Lymphocyte
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Homeostasis / immunology*
  • Humans
  • Infant
  • Ki-67 Antigen / analysis
  • Lymphopenia
  • Multivariate Analysis
  • Myeloablative Agonists / therapeutic use
  • Prognosis
  • Prospective Studies
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / physiology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / physiology*
  • Time Factors
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods


  • Ki-67 Antigen
  • Myeloablative Agonists