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 prim ed/memory phenotype and by reverse CD4/CD8 proportions. T lymphocytes from 26 BMT patients (mostly adults) were obtained at various times after transp lantation (from 45 to greater than or equal to 730 days) and were tested fo r susceptibility to spontaneous apoptosis and anti-fas triggered apoptosis in vitro. Substantial proportions of CD4(+) and CD8(+) cells generated duri ng the first year after transplantation, but not by day 730, exhibited in t hese assays der creased mitochondrial membrane potential(Delta Psi m) and a poptotic DNA fragmentation. The apoptotic phenotype tended to disappear lat e in the follow-up period, when substantial absolute numbers of naive (CD45 RA+/CD62-L+)T cells had repopulated the peripheral blood compartment of the BMT patients. The rate of spontaneous cell death in vitro was significantl y correlated with lower levels of ex vivo Bcl-2 protein, as assessed by cyt ofluorometry and Western blot analysis. In contrast, the levels of Bar prot ein remained unchanged, resulting in dysregulated Bcl-2/Bax ratios. Cell de ath primarily concerned the expanded CD8(+)/CD45R0(+) subpopulation, althou gh CD45R0(-) subpopulations were also involved, albeit to a lesser extent. These results show that the T-cell regeneration/expansion occurring after B MT is accompanied by decreased levels of Bcl-2 and susceptibility to apopto sis. (C) 1999 by The American Society of Hematology.