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Stepwise Development of Committed Progenitors in the Bone Marrow That Generate Functional T Cells in the Absence of the Thymus¹

Marcos E. García-Ojeda^2,*, Sussan Dejbakhsh-Jones^2,*, Devavani Chatterjea-Matthes^*, Aditi Mukhopadhyay^*, Andrew BitMansour^*, Irving L. Weissman, Janice M. Y. Brown^* and Samuel Strober^3,*

^* Department of Medicine and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305

We identified committed T cell progenitors (CTPs) in the mouse bone marrow that have not rearranged the TCR gene; express a variety of genes associated with commitment to the T cell lineage, including GATA-3, T cell-specific factor-1, C, and Id2; and show a surface marker pattern (CD44⁺CD25^–CD24⁺CD5^–) that is similar to the earliest T cell progenitors in the thymus. More mature committed intermediate progenitors in the marrow have rearranged the TCR gene loci, express V and V genes as well as CD3, but do not express surface TCR or CD3 receptors. CTPs, but not progenitors from the thymus, reconstituted the T cells in the lymphoid tissues of athymic nu/nu mice. These reconstituted T cells vigorously secreted IFN- after stimulation in vitro, and protected the mice against lethal infection with murine CMV. In conclusion, CTPs in wild-type bone marrow can generate functional T cells via an extrathymic pathway in athymic nu/nu mice.

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