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 beta gene; express a variety of genes associated with commitment to the T cell lineage, including GATA-3, T cell-specific factor-1, C beta, 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 alpha and V beta genes as well as CD3 epsilon, but do not express surface TCR or CD3 receptors. CTPs, but not progenitors from the thymus, reconstituted the alpha beta T cells in the lymphoid tissues of athymic nu/nu mice. These reconstituted T cells vigorously secreted IFN-gamma 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.