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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3511-3519.
Prepublished online as a Blood First Edition Paper on January 5, 2006; DOI 10.1182/blood-2005-08-3454.
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HEMATOPOIESIS
Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation
Ivan Maillard,
Benjamin A. Schwarz,
Arivazhagan Sambandam,
Terry Fang,
Olga Shestova,
Lanwei Xu,
Avinash Bhandoola, and
Warren S. Pear
From the Division of Hematology-Oncology, Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA.
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.
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