Competition for T cell progenitor niches in the thymus. (A) A schematic depiction of early thymocyte development. Incoming lymphoid progenitors home to the thymic rudiment, where they are sequentially exposed to stromal factors (e.g., SCF, IL-7, CXCL12, and DLL4) in different types of niches, here designated by the stage of thymocytes occupying them. (B) After transplantation into a wild-type (WT) host, thymocytes in the donor thymus are competitively replaced by a continuous stream of host-derived progenitor cells. Host-derived progenitor cells are outlined in blue. (C) Transplantation of WT thymi into hosts bearing different mutations alters the outcome of intrathymic T cell development. In Rag2^−/− hosts, host progenitor cells competitively replace donor thymocytes in DN1, DN2, and DN3 niches even though host thymocytes fail to generate a functional pre–TCR or TCR. In Rag2^−/−Il7r^−/− hosts, competitive replacement is restricted to DN1 and DN2 niches. Additional abrogation of SCF signaling eliminates competition in all niches, perhaps facilitating donor thymocyte occupancy of inappropriate niches. In the latter two situations, sustained generation of donor T cells occurs in the WT thymus graft.