Reconstitution of dendritic and natural killer–cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand
| Autor: | Alois Gratwohl, Elena Chklovskaia, Aleksandra Wodnar-Filipowicz, Catherine Nissen, Mario Bargetzi, Pegah Nowbakht |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Cytotoxicity Immunologic Adolescent Immunology Graft vs Host Disease Stem cell factor Biology Biochemistry Immunophenotyping Natural killer cell Interleukin 21 medicine Humans Regeneration Transplantation Homologous Cell Lineage Lymphokine-activated killer cell Graft Survival Hematopoietic Stem Cell Transplantation Membrane Proteins Dendritic Cells Cell Biology Hematology Middle Aged Killer Cells Natural Transplantation Kinetics medicine.anatomical_structure Interleukin 15 Hematologic Neoplasms Cyclosporine Myeloid-derived Suppressor Cell Cytokines Stem cell |
| Zdroj: | Blood. 103:3860-3868 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2003-04-1200 |
| Popis: | Recovery of dendritic cells (DCs) and natural killer (NK) cells after allogeneic stem cell transplantation (SCT) is important for allograft responses and antitumor immunity and thus for treatment outcome. Regulation of this regenerative process is not well understood. We investigated the influence of endogenous cytokines on the recovery and diversification of DC and NK cell subsets up to 6 months after SCT. Reconstitution of circulating DCs and NK cells was rapid but accompanied by prolonged skewing of cell subsets. The speed of recovery of CD11c+CD123low DC1 exceeded that of CD11c– CD123+ DC2, and correlated with plasma levels of flt3 ligand (FL), but not with granulocyte or granulocyte-macrophage colony-stimulating factors and stem cell factor. There was a 5-fold increase in interferon-γ–producing CD56highCD16–/low NK cells and a corresponding reduction in the CD56lowCD16high subset, accompanied by strongly reduced NK cell cytotoxicity. In vitro data implicate an inhibitory effect of cyclosporin A on NK cell differentiation and cytotoxicity. NK cell numbers did not correlate with plasma levels of FL or interleukin 15. Our results demonstrate that endogenous FL has distinct effects on the kinetics of reconstitution of DCs and NK cells and have potential implications for the modulation of immune responses after allogeneic SCT. |
| Databáze: | OpenAIRE |
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