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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2001-11-0005.
Submitted December 18, 2001
Pediatric Stem Cell Transplant Program, University of Tuebingen, Tuebingen, Germany * Corresponding author; email: p-g.schlegel{at}med.uni-tuebingen.de.
Normalization of restricted T-cell receptor (TCR) repertoire is critical following T-cell-depleted (TCD) stem cell transplantation. We present a prospective study analyzing respective contributions of naive and memory T-cell subsets within the CD4+ and CD8+ compartments to the evolution of overall TCR-repertoire complexity following transplantation of CD34-selected peripheral blood progenitor cells from unrelated donors. During the first post-transplant year, sorted CD4/45RA, CD4/45R0, CD8/45RA and CD8/45R0 subsets were analyzed at three monthly intervals for TCR-repertoire complexity by CDR3-size-spectratyping. Skew in TCR-repertoire was observed only in early memory-type T-cells. CD4+ and CD8+ subsets differed in clonal distribution of CDR3-sizes, with rapid Gaussian normalization of bands in CD4/45R0+ T-cells. Naive T-cells displayed normal repertoire complexity and contributed significantly to skew correction. Our data provides direct evidence for an important role of de novo-maturation of naive T-cells in normalization of an initially restricted TCR-repertoire following transplantation of CD34-selected, TCD peripheral blood progenitors from unrelated donors.
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