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Polyclonal T-cell reconstitution of X-SCID recipients after in utero transplantation of lymphoid-primed multipotent progenitors

In English

Författare

Summary, in English

Although successful in utero hematopoietic cell transplantation (IUHCT) of X-linked severe combined immune deficiency (X-SCID) with enriched stem and progenitor cells was achieved more than a decade ago, it remains applied only in rare cases. Although this in part reflects that postnatal transplantations have overall given good results, there are no direct comparisons between IUHCT and postnatal transplantations of X-SCID. The proposed tolerance of the fetal immune system to foreign human leukocyte antigen early in gestation, a main rationale behind IUHCT, has recently been challenged by evidence for a considerable immune barrier against in utero transplanted allogeneic bone marrow cells. Consequently, there is need for further exploring the application of purified stem and progenitor cells to overcome this barrier also in IUHCT. Herein, we demonstrate in a congenic setting that recently identified lymphoid-primed multipotent progenitors are superior to hematopoietic stem cells in providing rapid lymphoid reconstitution after IUHCT of X-SCID recipients, and sustain in the long-term B cells, polyclonal T cells, as well as short-lived B-cell progenitors and thymic T-cell precursors. We further provide evidence for IUHCT of hematopoietic stem cells giving superior B- and T-cell reconstitution in fetal X-SCID recipients compared with neonatal and adolescent recipients. (Blood. 2009;113:4790-4798)

Publiceringsår

2009

Språk

Engelska

Sidor

4790-4798

Publikation/Tidskrift/Serie

Blood

Volym

113

Issue

19

Dokumenttyp

Artikel i tidskrift

Förlag

American Society of Hematology

Ämne

  • Cell and Molecular Biology

Status

Published

Forskningsgrupp

  • Immunology
  • Brain Repair and Imaging in Neural Systems (BRAINS)

ISBN/ISSN/Övrigt

  • ISSN: 1528-0020