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

We identified committed T cell progenitors (CTPs) in the mouse bone marrow that have not rearranged the TCR β gene, express a variety of genes associated with commitment to the T cell lineage including GATA-3 and TCF-1, C_βand 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 (CIPs) in the marrow have rearranged the TCR gene loci, express V_αand V_βgenes as well as CD3_ε, but do not express surface TCR or CD3 receptors. CTPs, but not progenitors from the thymus, reconstituted the αβ T cells in the lymphoid tissues of athymic nu/nu mice. These reconstituted T cells vigorously secreted IFN- γ after stimulation in vitro, and protected the mice against lethal infection with murine cytomegalovirus (MCMV). Also CTPs from the parent strain can reconstitute an F1 MHC haplotype mismatched host. In conclusion, CTPs in wild-type bone marrow can generate functional T cells via an extrathymic pathway.