Interleukin‐7 in the transition of bone marrow progenitors to the thymus

Interleukin‐7 (IL‐7) is essential for the development of T cells in humans and mice where deficiencies in IL‐7 signaling result in severe immunodeficiency. T cells require IL‐7 at multiple points during development; however, it is unclear when IL‐7 is first necessary. We observed that mice with impaired IL‐7 signaling had a large reduction in the number of early thymic progenitors (ETPs) while mice that overexpress IL‐7 had greatly increased numbers of ETPs. These results indicated that the development of ETPs is sensitive to IL‐7. Bone marrow progenitors of ETP are present in normal numbers in mice with impaired IL‐7 signaling (IL‐7Rα 449F ) and were efficiently recruited to the thymus. Furthermore, ETPs and their progenitors from IL‐7Rα 449F mice did not undergo increased apoptosis and proliferate normally compared to WT cells. Mixed bone marrow chimeras demonstrated that IL‐7 signaling has a cell‐intrinsic role in ETP development but was not required for development of bone marrow progenitors. We have shown a novel role for IL‐7 signaling in the development of ETPs that is distinct from classic mechanisms of IL‐7 regulating survival and proliferation.