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Early Defect Prethymic in Bone Marrow T Cell Progenitors in Athymic nu/nu Mice ¹

Devavani Chatterjea-Matthes^*, Marcos E. García-Ojeda^*, Sussan Dejbakhsh-Jones^*, Libuse Jerabek, Markus G. Manz, Irving L. Weissman and Samuel Strober^2,*

Department of ^* Medicine, Division of Immunology and Rheumatology and Department of Pathology, Stanford University, Stanford, CA 94305

nu/nu mice fail to develop a thymus and mature T cells due to a defect in the whn gene encoding a transcription factor necessary for terminal epithelial cell differentiation. We investigated whether early T cell progenitor development in the nu/nu bone marrow is also defective. We demonstrated a maturation arrest of nu/nu marrow T cell progenitors associated with a lack of pT gene expression and a failure to give rise to mature T cells in adoptive euthymic hosts. Wild-type hemopoietic stem cells rapidly matured into functional T cell progenitors in the marrow of euthymic or thymectomized but not nu/nu hosts. We show that defects in bone marrow prethymic T cell development can also contribute to T cell deficiency in nu/nu mice.

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