title: Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy.
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 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.
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada; Département de Sciences Biomédicales, Université de Montréal, Québec, Canada.
authors.forename: Emily
authors.initials: E
authors.lastname: Charrier
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada.
authors.forename: Paulo
authors.initials: P
authors.lastname: Cordeiro
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Brito
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada; Département de Microbiologie et d'Immunologie, Université de Montréal, Québec, Canada.
authors.forename: Michaël
authors.initials: M
authors.lastname: Harnois
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada.
authors.forename: Samira
authors.initials: S
authors.lastname: Mezziani
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada.
authors.forename: Sabine
authors.initials: S
authors.lastname: Herblot
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada; Département de Microbiologie et d'Immunologie, Université de Montréal, Québec, Canada; Département de Pédiatrie, Université de Montréal, Québec, Canada.
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.affiliation: Groupe de Recherche en Transplantation et Immunologie du Sang de Cordon (GRETISC), Centre de Cancérologie Charles Bruneau, Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada; Département de Sciences Biomédicales, Université de Montréal, Québec, Canada; Département de Microbiologie et d'Immunologie, Université de Montréal, Québec, Canada; Département de Pédiatrie, Université de Montréal, Québec, Canada. Electronic address: michel.duval@umontreal.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Duval
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002452:Cell Count; D049109:Cell Proliferation; D002648:Child; D036101:Cord Blood Stem Cell Transplantation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D000961:Antilymphocyte Serum; C526902:CpG ODN 2216; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: Cord blood transplantation; Interferon-alpha; Plasmacytoid dendritic cells; Toll-like receptor (TLR)-9 agonist