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Lancet. 2000 May 27;355(9218):1875-81.

Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution.

Author information

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390, USA. daniel.douek@mednet.swmed.edu

Abstract

BACKGROUND:

The potential benefits of haematopoietic stem-cell transplantation are tempered by the depletion of T-cells accompanying this procedure. We used a new technique which quantifies the excisional DNA products of T-cell-receptor (TCR) gene rearrangement to measure thymic output directly in patients with multiple myeloma, and thus assessed the contribution of the thymus to immune recovery after transplantation.

METHODS:

We studied 40 patients, 34-66 years of age, who had been randomly assigned myeloablative chemotherapy and autologous peripheral-blood haematopoietic stem-cell transplantation with unmanipulated grafts or grafts enriched for CD34 stem cells. CD4 and CD8 T-cell counts were measured, thymic output was estimated serially until 2 years after transplantation, and percentages of naive T-cells were measured.

FINDINGS:

The production of substantial numbers of new naive T cells by the thymus could be detected by 100 days post-transplant; there was a significant inverse relation between age and recovery of new T cells. In the CD34-unselected group, numbers of TCR-rearrangement excision circles returned to baseline after 2 years, whereas in the CD34-selected group, numbers at 2 years were significantly higher than both baseline numbers (p=0.004), and 2-year numbers in the unselected group (p=0.046). Increased thymic output correlated with, and was predictive of, increased naive T-cell numbers and broader T-cell-receptor repertoires.

INTERPRETATION:

Our results provide evidence that the adult thymus contributes more substantially to immune reconstitution after haematopoietic stem-cell transplantation than was previously thought, and therefore could be a target for therapeutic intervention.

PMID:
10866444
[PubMed - indexed for MEDLINE]
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