Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy
| Autor: | Rose-Marie Brito, Michel Duval, Françoise Le Deist, Michaël Harnois, Emily Charrier, Sabine Herblot, Paulo Cordeiro, Samira Mezziani |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Adoptive cell transfer Transplantation Conditioning Cord blood transplantation Adolescent medicine.medical_treatment Alpha interferon Gene Expression Graft vs Host Disease Cell Count Immune system Antigens CD medicine Toll-like receptor (TLR)-9 agonist Humans Transplantation Homologous Longitudinal Studies Child Antilymphocyte Serum Bone Marrow Transplantation Cell Proliferation Transplantation Leukemia business.industry Interferon-alpha hemic and immune systems Hematology Immunotherapy Dendritic Cells surgical procedures operative medicine.anatomical_structure Plasmacytoid dendritic cells Oligodeoxyribonucleotides Cord blood Toll-Like Receptor 9 Immunology Female Bone marrow Cord Blood Stem Cell Transplantation business Interferon-alpha production Immunosuppressive Agents |
| Zdroj: | Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 20(10) |
| ISSN: | 1523-6536 |
| Popis: | Plasmacytoid dendritic cells (pDCs) initiate both innate and adaptive immune responses, making them attractive targets for post-transplantation immunotherapy, particularly after cord blood transplantation (CBT). Toll-like receptor (TLR) agonists are currently studied for pDC stimulation in various clinical settings. Their efficacy depends on pDC number and functionality, which are unknown after CBT. We performed a longitudinal study of pDC reconstitution in children who underwent bone marrow transplantation (BMT) and single-unit CBT. Both CBT and unrelated BMT patients received antithymocyte globulin as part of their graft-versus-host disease prophylaxis regimen. pDC blood counts were higher in CBT patients than in healthy volunteers from 2 to 9 months after transplantation, whereas they remained lower in BMT patients. We showed that cord blood progenitors gave rise in vitro to a 500-fold increase in functional pDCs over bone marrow counterparts. Upon stimulation with a TLR agonist, pDCs from both CBT and BMT recipients upregulated T cell costimulatory molecules, whereas interferon-alpha (IFN-α) production was impaired for 9 months after CBT. TLR agonist treatment is thus not expected to induce IFN-α production by pDCs after CBT, limiting its immunotherapeutic potential. Fortunately, in vitro production of large amounts of functional pDCs from cord blood progenitors paves the way for the post-transplantation adoptive transfer of pDCs. |
| Databáze: | OpenAIRE |
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