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PMID: 16397133 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation.

Blood ·Vol. 107 ·No. 9 ·2006-05-01 ·Pages 3511-9

Maillard I, Schwarz BA, Sambandam A, Fang T, Shestova O, Xu L, Bhandoola A, Pear WS

Abstract

Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in adult mice, although alternative T-cell differentiation pathways may exist. While we were investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT), we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had been replenished. Simultaneously, T lineage-restricted progenitors were generated at extrathymic sites, both in the spleen and in peripheral lymph nodes, but not in the bone marrow or liver. The generation of these T lineage-committed cells occurred through a Notch-dependent differentiation process. Multipotent bone marrow progenitors efficiently gave rise to extrathymic T lineage-committed cells, whereas common lymphoid progenitors did not. Our data show plasticity of T-lineage commitment sites in the post-BMT environment and indicate that Notch-driven extrathymic Tlineage commitment from multipotent progenitors may contribute to early T-lineage reconstitution after BMT.

MeSH Terms
Animals Bone Marrow Transplantation Cell Differentiation Cell Line Female Hematopoietic Stem Cells/cytology,immunology,metabolism Mice Mice, Inbred C57BL Mice, Transgenic Receptors, Notch/metabolism Signal Transduction Spleen/cytology T-Lymphocytes/cytology,immunology,metabolism
Chemicals
Receptors, Notch
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Maillard Ivan
611 BRB II/III, 421 Curie Blvd, University of Pennsylvania, Philadelphia, PA 19104, USA.
Schwarz Benjamin A
Sambandam Arivazhagan
Fang Terry
Shestova Olga
Xu Lanwei
Bhandoola Avinash
Pear Warren S
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2005-08-3454
Published
2006-05-01
Epub
2006-00-05
Pages
3511-9
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895767
Subset
IM
Grants
NIAID NIH HHS · T32 AI055428 · United States
NIAID NIH HHS · R01 AI059621 · United States
NIAID NIH HHS · R01AI047833 · United States
NIAID NIH HHS · T32-AI-055428 · United States
External Links
PubMed source DOI: 10.1182/blood-2005-08-3454 PMC Full Text View journal details
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