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
| Autor: | O Déas, Bernard Charpentier, Nadia Chafika Hebib, Matthieu Rouleau, Anna Senik, Jean-Paul Vernant, Antoine Durrbach, Françoise Beaujean |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Programmed cell death T cell Immunology Apoptosis Biology Biochemistry Immunophenotyping Andrology T-Lymphocyte Subsets Transplantation Immunology medicine Humans Transplantation Homologous fas Receptor Bone Marrow Transplantation Apoptotic DNA fragmentation Cell Biology Hematology Fas receptor Transplantation medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Hematologic Neoplasms Bone marrow CD8 |
| Zdroj: | ResearcherID |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v94.5.1803.417a28_1803_1813 |
| Popis: | 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 (▵Ψm) 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. |
| Databáze: | OpenAIRE |
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