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T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants.

Te Boekhorst PA, Lamers CH, Schipperus MR, Hintzen RQ, van der Holt B, Cornelissen JJ, Löwenberg B, Gratama JW

1Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.

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(-) ( approximately 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-gamma, IL-2 and TNF-alpha 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.Bone Marrow Transplantation (2006) 37, 763-772. doi:10.1038/sj.bmt.1705333; published online 6 March 2006.

Published 5 April 2006 in Bone Marrow Transplant, 37(8): 763-72.
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