Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children
| Autor: | Michael Maschan, A. A. Maschan, Sofya A. Kasatskaya, Ivan V. Zvyagin, Mikhail Shugay, Ekaterina A. Komech, D.N. Balashov, O V Tatarinova, Anastasiia L. Sycheva, V.V. Brilliantova, E V Boyakova, Larisa Shelikhova, Y B Lebedev, Elena Kurnikova, Dmitry M. Chudakov, Ilgar Z. Mamedov |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Time Factors Adolescent Receptors Antigen T-Cell alpha-beta T-Lymphocytes T cell Antigens CD19 Biology Lymphocyte Depletion Young Adult 03 medical and health sciences 0302 clinical medicine Immune system Antigen medicine Humans Progenitor cell Child Graft Survival Hematopoietic Stem Cell Transplantation Infant Hematology medicine.disease Hematologic Diseases 3. Good health Transplantation Leukemia Haematopoiesis 030104 developmental biology medicine.anatomical_structure Oncology Child Preschool Immunology Stem cell 030215 immunology |
| Zdroj: | Leukemia. 31:1145-1153 |
| ISSN: | 1476-5551 0887-6924 |
| Popis: | αβT-cell-depleted allogeneic hematopoietic cell transplantation holds promise for the safe and accessible therapy of both malignant and non-malignant blood disorders. Here we employed molecular barcoding normalized T-cell receptor (TCR) profiling to quantitatively track T-cell immune reconstitution after TCRαβ-/CD19-depleted transplantation in children. We demonstrate that seemingly early reconstitution of αβT-cell counts 2 months after transplantation is based on only several hundred rapidly expanded clones originating from non-depleted graft cells. In further months, frequency of these hyperexpanded clones declines, and after 1 year the observed T-cell counts and TCRβ diversity are mostly provided by the newly produced T cells. We also demonstrate that high TCRβ diversity at day 60 observed for some of the patients is determined by recipient T cells and intrathymic progenitors that survived conditioning regimen. Our results indicate that further efforts on optimization of TCRαβ-/CD19-depleted transplantation protocols should be directed toward providing more efficient T-cell defense in the first months after transplantation. |
| Databáze: | OpenAIRE |
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