Polyclonal T cell reconstitution of X-SCID recipients following in utero transplantation of lymphoid-primed multipotent progenitors.
Nummer: Dec 12
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 over a decade ago, it remains applied only in rare cases. While 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 HLA 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 (BM) 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 (LMPPs) are superior to hematopoietic stem cells (HSCs) in providing rapid lymphoid reconstitution following 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 HSCs giving superior B and T cell reconstitution in fetal X-SCID recipients when compared to neonatal and adolescent recipients.
- Medicine and Health Sciences
- ISSN: 1528-0020