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

Bone Marrow Transplantation
P A W Te BoekhorstJ W Gratama

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(-) ( 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 suscepti...Continue Reading

References

Jun 18, 2002·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Harry OpenshawPeter A McSweeney
Jun 18, 2002·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Fulvio CrippaMichael Boeckh
Feb 25, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D DamianiR Fanin
Oct 28, 2004·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jan StorekDavid G Maloney
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Sep 5, 2008·Current Protocols in Cytometry·D Robert SutherlandJan W Gratama

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Citations

Jun 12, 2013·Human Immunology·Kristian AssingNiels Fisker
Mar 7, 2013·Annals of Neurology·Peter J DarlingtonUNKNOWN Canadian MS/BMT Study Group
Apr 1, 2008·Hematology/oncology and Stem Cell Therapy·Lucille WoodPeter Jacobs

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