Polyclonal T-cell reconstitution of X-SCID recipients after in utero transplantation of lymphoid-primed multipotent progenitors
Autor: | Karina Liuba, Simon R.W. Stott, Sten Eirik W. Jacobsen, Cornelis J.H. Pronk |
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Jazyk: | angličtina |
Rok vydání: | 2009 |
Předmět: |
T-Lymphocytes
Immunology Mice SCID Thymus Gland Biology X-Linked Combined Immunodeficiency Diseases Biochemistry In utero transplantation Mice Fetus Bone Marrow medicine Animals Myeloid Cells Lymphopoiesis Progenitor cell Gene Rearrangement Severe combined immunodeficiency Multipotent Stem Cells Stem Cells Uterus fungi Cell Biology Hematology Lymphoid Progenitor Cells Hematopoietic Stem Cells medicine.disease Mice Inbred C57BL medicine.anatomical_structure Animals Newborn Multipotent Stem Cell Female Bone marrow Stem cell |
Zdroj: | Blood. 113(19) |
ISSN: | 1528-0020 0006-4971 |
Popis: | 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. |
Databáze: | OpenAIRE |
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