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

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Abstract

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)

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  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)4790-4798
JournalBlood
Volume113
Issue number19
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes

Related research output

Liuba, K., 2009, Department of Obstetrics and Gynecology, Lund University. 71 p.

Research output: ThesisDoctoral Thesis (compilation)

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