Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children
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Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children. / Eyrich, Matthias; Wollny, Gernot; Tzaribaschev, Nikolaj; Dietz, Klaus; Brügger, Dorothee; Bader, Peter; Lang, Peter; Schilbach, Karin; Winkler, Beate; Niethammer, Dietrich; Schlegel, Paul G.
In: BIOL BLOOD MARROW TR, Vol. 11, No. 3, 03.2005, p. 194-205.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children
AU - Eyrich, Matthias
AU - Wollny, Gernot
AU - Tzaribaschev, Nikolaj
AU - Dietz, Klaus
AU - Brügger, Dorothee
AU - Bader, Peter
AU - Lang, Peter
AU - Schilbach, Karin
AU - Winkler, Beate
AU - Niethammer, Dietrich
AU - Schlegel, Paul G
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Cell Proliferation
KW - Child
KW - Child, Preschool
KW - Cohort Studies
KW - Gene Rearrangement, T-Lymphocyte
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Homeostasis/immunology
KW - Humans
KW - Infant
KW - Ki-67 Antigen/analysis
KW - Lymphopenia
KW - Multivariate Analysis
KW - Myeloablative Agonists/therapeutic use
KW - Prognosis
KW - Prospective Studies
KW - T-Lymphocyte Subsets/immunology
KW - T-Lymphocytes/cytology
KW - Thymus Gland/cytology
KW - Time Factors
KW - Transplantation Conditioning/adverse effects
U2 - 10.1016/j.bbmt.2004.12.001
DO - 10.1016/j.bbmt.2004.12.001
M3 - SCORING: Journal article
C2 - 15744238
VL - 11
SP - 194
EP - 205
JO - BIOL BLOOD MARROW TR
JF - BIOL BLOOD MARROW TR
SN - 1083-8791
IS - 3
ER -