T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants
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 susceptibility to apoptosis would interfere with a swift and sustained CD4(+) T-cell regeneration post SCT.
|Keywords||Adult, Antigens, CD27/biosynthesis, Antigens, CD3/biosynthesis, Antigens, CD4/biosynthesis, Antigens, CD45/biosynthesis, Antigens, CD95/biosynthesis, Apoptosis, CD4-Positive T-Lymphocytes/metabolism, CD8-Positive T-Lymphocytes/metabolism, Cytokines/metabolism, Female, Humans, Immune System/metabolism, Interferon-gamma/metabolism, Interleukin-2/metabolism, Kinetics, L-Selectin/biosynthesis, Lymphocytes/metabolism, Middle Aged, Multiple Sclerosis/*blood/*therapy, Neutrophils/metabolism, T-Lymphocytes/immunology/*metabolism, Time Factors, Transplantation Conditioning, male|
|Persistent URL||dx.doi.org/10.1038/sj.bmt.1705333, hdl.handle.net/1765/21823|
Boekhorst, P.A.W., Lamers, C.H.J., Schipperus, M.R., Hintzen, R.Q., van der Holt, B., Cornelissen, J.J., … Gratama, J.W.. (2006). T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants. Bone Marrow Transplantation, 37(8), 763–772. doi:10.1038/sj.bmt.1705333