Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children.
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.
Eyrich
Matthias
M
Children's Hospital, Pediatric Stem Cell Transplant Program, University of Tübingen, Germany. Eyrich_M@klinik.uni-wuerzburg.de
Wollny
Gernot
G
Tzaribaschev
Nikolaj
N
Dietz
Klaus
K
Brügger
Dorothee
D
Bader
Peter
P
Lang
Peter
P
Schilbach
Karin
K
Winkler
Beate
B
Niethammer
Dietrich
D
Schlegel
Paul G
PG
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
D019394:Ki-67 Antigen; D019653:Myeloablative Agonists