Original Article
Bone Marrow Transplantation (2006) 37, 763–772. doi:10.1038/sj.bmt.1705333; published online 6 March 2006
Post-Transplant Events
T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants
P A W te Boekhorst1, C H J Lamers2, M R Schipperus3, R Q Hintzen4, B van der Holt5, J J Cornelissen1, B Löwenberg1 and J W Gratama2
- 1Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands
- 2Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
- 3Department of Hematology, HAGA Hospitals, The Hague, The Netherlands
- 4Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
- 5Department of Trials & Statistics, Erasmus Medical Center, Rotterdam, The Netherlands
Correspondence: Dr PAW te Boekhorst, Department of Hematology, Erasmus Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: p.teboekhorst@erasmusmc.nl
Received 30 August 2005; Revised 2 February 2006; Accepted 3 February 2006; Published online 6 March 2006.
Abstract
We compared the kinetics of T-cell recovery after extensive ex vivo and in vivo T-cell depleted autologous stem cell transplantation (SCT) for multiple sclerosis (MS; n=8) with unmodified SCT for hematological malignancies (HM; n=39). Both patient group showed a very protracted recovery of 'naive' CD4+, 45R0- (
CD45RA+) T-cells. Within the 'primed' CD4+, 45R0+ T-cells, the 'central memory' cells expressing the CD62L and CD27 markers were the slowest to recover. The repopulating T-cells were highly activated, as shown by increased expression of HLA-DR and the apoptosis marker CD95. The capability of CD4+ and CD8+ T-cells to produce IFN-
, IL-2 and TNF-
had reached normal ranges from 2 months post SCT onwards. Unexpectedly, the kinetics of T-cell recovery between 3 and 12 months post transplant was similar in T-depleted and unmodified SCT. Before SCT, the HM patients showed lymphopenia of all T-cell subsets, upregulated HLA-DR and CD95 expression and increased cytokine responses. We suggest that the similar kinetics of T-cell recovery in the two patient groups may be explained by the susceptibility to apoptosis of the activated CD4+ T-cells in the autografts of the HM patients. This susceptibility to apoptosis would interfere with a swift and sustained CD4+ T-cell regeneration post SCT.
Keywords:
autologous stem cell transplantation, T-cell depletion, T lymphocytes, immune reconstitution
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