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Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy.


PMID 25128615

Abstract

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 9xa0months after transplantation, whereas they remained lower in BMT patients. We showed that cord blood progenitors gave rise inxa0vitro 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 Txa0cell costimulatory molecules, whereas interferon-alpha (IFN-α) production was impaired for 9xa0months after CBT. TLR agonist treatment is thus not expected to induce IFN-α production by pDCs after CBT, limiting its immunotherapeutic potential. Fortunately, inxa0vitro production of large amounts of functional pDCs from cord blood progenitors paves the way for the post-transplantation adoptive transfer of pDCs.