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      Cord blood transplantation recapitulates fetal ontogeny with a distinct molecular signature that supports CD4+ T-cell reconstitution.

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          Abstract

          Omission of in vivo T-cell depletion promotes rapid, thymic-independent CD4+-biased T-cell recovery after cord blood transplant. This enhanced T-cell reconstitution differs from that seen after stem cell transplant from other stem cell sources, but the mechanism is not known. Here, we demonstrate that the transcription profile of naive CD4+ T cells from cord blood and that of lymphocytes reconstituting after cord blood transplantation is similar to the transcription profile of fetal CD4+ T cells. This profile is distinct to that of naive CD4+ T cells from peripheral blood and that of lymphocytes reconstituting after T-replete bone marrow transplantation. The transcription profile of reconstituting naive CD4+ T cells from cord blood transplant recipients was upregulated in the T-cell receptor (TCR) signaling pathway and its transcription factor activator protein-1 (AP-1). Furthermore, a small molecule inhibitor of AP-1 proportionally inhibited cord blood CD4+ T-cell proliferation (P < .05). Together, these findings suggest that reconstituting cord blood CD4+ T cells reflect the properties of fetal ontogenesis, and enhanced TCR signaling is responsible for the rapid restoration of the unique CD4+ T-cell biased adaptive immunity after cord blood transplantation.

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          Author and article information

          Journal
          Blood Adv
          Blood advances
          American Society of Hematology
          2473-9529
          2473-9529
          Nov 14 2017
          : 1
          : 24
          Affiliations
          [1 ] Molecular and Cellular Immunology Section, University College London Institute of Child Health, London, United Kingdom.
          [2 ] Department of Haematology and Bone Marrow Transplantation, Royal Manchester Children's Hospital, Manchester, United Kingdom.
          [3 ] Genetics and Genomic Medicine Programme, University College London Institute of Child Health, London, United Kingdom.
          [4 ] Department of Immunology.
          [5 ] Department of Bone Marrow Transplantation, and.
          [6 ] Laboratory Immunology, Great Ormond Street Hospital for Children, London, United Kingdom.
          [7 ] Anthony Nolan Research Institute, London, United Kingdom; and.
          [8 ] University College London Cancer Institute, Royal Free Campus, London, United Kingdom.
          Article
          2017/010827
          10.1182/bloodadvances.2017010827
          5737134
          29296868
          5feeef0a-84bc-40a5-b3ab-c7e8ecbb3f74
          History

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