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Primitive Lymphoid Progenitors in Bone Marrow with T Lineage Reconstituting Potential¹

S. Scott Perry^2,*, Robert S. Welner^2,*,, Taku Kouro^*, Paul W. Kincade^3,* and Xiao-Hong Sun^*

^* Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; and Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

Multiple subsets of the bone marrow contain T cell precursors, but it remains unclear which is most likely to replenish the adult thymus. Therefore, RAG-1⁺ early lymphoid progenitors (RAG-1⁺ ELP), and CD62L/L-selectin⁺ progenitors (LSP), as well as common lymphoid progenitors from C57BL6-Thy1.1-RAG-1/GFP mouse bone marrow were directly compared in transplantation assays. The two c-Kit^high populations vigorously regenerated the thymus and were superior to common lymphoid progenitors in magnitude and frequency of thymic reconstitution. Regeneration was much faster than the 22 days described for transplanted stem cells, and RAG-1⁺ ELP produced small numbers of lymphocytes within 13 days. As previously reported, LSP were biased to a T cell fate, but this was not the case for RAG-1⁺ ELP. Although RAG-1⁺ ELP and LSP had reduced myeloid potential, they were both effective progenitors for T lymphocytes and NK cells. The LSP subset overlapped with and included most RAG-1⁺ ELP and many RAG-1^–TdT⁺ ELP. LSP and RAG-1⁺ ELP were both present in the peripheral circulation, but RAG-1⁺ ELP had no exact counterpart among immature thymocytes. The most primitive of thymocytes were similar to Lin^–c-Kit^highL-selectin⁺TdT⁺RAG-1^– progenitors present in the marrow, suggesting that this population is normally important for sustaining the adult thymus.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI 33597 and AI 056129 (to X.-H.S.), AI 20069 and AI 58162 (to P.W.K.), and T32-AI 07633 (to S.S.P.). X.-H.S. holds the Eli Lilly Distinguished Chair in Biomedical Research, and P.W.K. holds the William H. and Rita Bell Chair in Biomedical Research.

² S.S.P. and R.S.W. contributed equally to this study.

³ Address correspondence to Dr. Paul W. Kincade, Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104. E-mail address: kincade{at}omrf.ouhsc.edu

⁴ Abbreviations used in this paper: HSC, hemopoietic stem cell; LSK, Lin^–Sca1⁺c-Kit^high; ELP, early lymphoid progenitor (Lin^–Sca1⁺c-Kit^highRAG-1/GFP⁺); LSP, L-selectin⁺ progenitor (Lin^–Sca1⁺c-Kit^highThy1.1^–L-selectin⁺); CLP, common lymphoid progenitor (Lin^–Sca1^lowc-Kit^lowThy1.1^–IL-7R⁺); ETP, early thymic progenitor; DN, double negative.

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