A transgenic T cell receptor restores thymocyte differentiation in interleukin‐7 receptor α chain‐deficient mice

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Abstract
Interleukin‐7 (IL‐7) receptor α chain‐deficient (IL‐7Rα‐/‐) mice have severely depleted lymphocyte populations and thymocyte development is arrested at the double‐negative (DN) stage. We show that thymocyte development in these mice can be reconstituted by the introduction of a transgenic T cell receptor (TCR), implying that one function of the IL‐7Rα chain is to initiate TCR gene rearrangement. Expression of the recombinase‐activating genes RAG1 and RAG2 was greatly reduced in the IL‐7Rα‐/‐ thymuses, and in DN thymocytes from the TCR transgenic IL‐7Rα‐/‐ mice, but was restored in double‐positive thymocytes from the TCR transgenic IL‐7Rα‐/‐ mice. These data suggest that the IL‐7Rα chain controls RAG expression and initiation of TCRβ chain VDJ rearrangement in DN cells. In contrast, once cells have progressed beyond the DN stage of development the IL‐7Rα chain becomes no longer essential for RAG expression.