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.