T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants.
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.
Te Boekhorst
P A W
PA
Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands. p.teboekhorst@erasmusmc.nl
Lamers
C H J
CH
Schipperus
M R
MR
Hintzen
R Q
RQ
van der Holt
B
B
Cornelissen
J J
JJ
Löwenberg
B
B
Gratama
J W
JW
D000328:Adult; D017209:Apoptosis; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007700:Kinetics; D019041:L-Selectin / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000628:therapy*; D009504:Neutrophils / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous / Q000379:methods*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis; D019014:fas Receptor / Q000096:biosynthesis
D017252:CD3 Complex; D015704:CD4 Antigens; D016207:Cytokines; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor; D019041:L-Selectin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens