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.
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 (triangle upPsim) 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.
Hebib
N C
NC
UPR 420 of CNRS, Villejuif, France.
Déas
O
O
Rouleau
M
M
Durrbach
A
A
Charpentier
B
B
Beaujean
F
F
Vernant
J P
JP
Senik
A
A
D000328:Adult; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D019014:fas Receptor
D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor