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Blood, Vol. 94 No. 5 (September 1), 1999:
pp. 1803-1813
Peripheral Blood T Cells Generated After Allogeneic Bone Marrow
Transplantation: Lower Levels of Bcl-2 Protein and Enhanced Sensitivity
to Spontaneous and CD95-Mediated Apoptosis In Vitro. Abrogation of the
Apoptotic Phenotype Coincides With the Recovery of Normal Naive/Primed
T-Cell Profiles
Nadia Chafika Hebib,
Olivier Déas,
Matthieu Rouleau,
Antoine Durrbach,
Bernard Charpentier,
Françoise Beaujean,
Jean-Paul Vernant, and
Anna Senik
From the UPR 420 of CNRS, Villejuif, the Service d'Hématologie
Clinique, and the Centre de Transfusion Sanguine, Hôpital Henri
Mondor, Créteil, France.
T-cell reconstitution after bone marrow transplant (BMT) is
characterized, for at least 1 year, by the expansion of populations of
T cells with a primed/memory phenotype and by reverse CD4/CD8 proportions. T lymphocytes from 26 BMT patients (mostly adults) were
obtained at various times after transplantation (from 45 to  730
days) and were tested for susceptibility to spontaneous apoptosis and
anti-Fas triggered apoptosis in vitro. Substantial proportions of
CD4+ and CD8+ cells generated during the
first year after transplantation, but not by day 730, exhibited in
these assays decreased mitochondrial membrane potential (  m) and
apoptotic DNA fragmentation. The apoptotic phenotype tended to
disappear late in the follow-up period, when substantial absolute
numbers of naive (CD45RA+/CD62-L+) T
cells had repopulated the peripheral blood compartment of the BMT
patients. The rate of spontaneous cell death in vitro was significantly
correlated with lower levels of ex vivo Bcl-2 protein, as assessed by
cytofluorometry and Western blot analysis. In contrast, the levels of
Bax protein remained unchanged, resulting in dysregulated Bcl-2/Bax
ratios. Cell death primarily concerned the expanded
CD8+/CD45R0+ subpopulation, although
CD45R0 subpopulations were also involved, albeit to a
lesser extent. These results show that the T-cell
regeneration/expansion occurring after BMT is accompanied by decreased
levels of Bcl-2 and susceptibility to apoptosis.
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