Summary:
Positively selected CD34+ hematopoietic stem cells from unrelated donors (UD-HSCT) have been successfully transplanted, but little is known about immune reconstitution in this setting. Here we report a prospective comparison of immune reconstitution in recipients of UD-HSCT and of unmanipulated bone marrow from matched sibling donors (MSD-BMT). T-cell reconstitution occurred more than 100 days later in the UD-HSCT than in the MSD-BMT group. The first T cells after UD-HSCT were almost exclusively CD45RO+ HLA-DR+, whereas early-emerging T cells after MSD-BMT more frequently expressed CD62L, CD28, and CD25. In both groups, numbers of CD45RA+ naive T cells increased after 180 days. After UD-HSCT, the T-cell-receptor (TCR)-repertoire was severely skewed and showed significantly reduced diversity during the first year, but only minor abnormalities were seen after MSD-BMT. TCR-diversity increased simultaneously with the number of naive T cells. In both groups, we observed transient expansions of γδ T cells. B cells were reconstituted more rapidly in UD-HSCT than in MSD-BMT recipients, whereas the rapidity of NK-cell reconstitution was similar in the two groups. In summary, T-cell reconstitution was slower after UD-HSCT than after MSD-BMT because of the delayed recovery of early memory-type T cells with reduced TCR-diversity, whereas naive T-, NK-, and B cells were reconstituted similarly in the two groups.
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Acknowledgements
We thank the staff of the BMT unit and outpatient department, as well as the technical staff of the stem cell processing unit, at the University Children's Hospital, Tübingen for their excellent and dedicated patient care. We also thank Sharon Naron for editorial assistance with the manuscript.
ME is the recipient of a postdoctoral fellowship awarded by the Else Übelmesser Foundation for Cancer Research (1.3-0415.221.18-03/97). This work was supported by a grant from the fortüne-Program of the University of Tübingen (#587/1999) and by Interdisciplinary Research Centre (IZKF) Program Project Grant IIA3 (1999–2002 to P.G.S.) of the University of Tübingen.
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Eyrich, M., Leiler, C., Lang, P. et al. A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors. Bone Marrow Transplant 32, 379–390 (2003). https://doi.org/10.1038/sj.bmt.1704158
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DOI: https://doi.org/10.1038/sj.bmt.1704158
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