A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor alpha chain-deficient mice.

Interleukin-7 (IL-7) receptor alpha chain-deficient (IL-7R alpha-/-) 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-7R alpha chain is to initiate TCR gene rearrangement. Expression of the recombinase-activating genes RAG1 and RAG2 was greatly reduced in the IL-7R alpha-/- thymuses, and in DN thymocytes from the TCR transgenic IL-7R alpha-/- mice, but was restored in double-positive thymocytes from the TCR transgenic IL-7R alpha-/- mice. These data suggest that the IL-7R alpha chain controls RAG expression and initiation of TCR beta chain VDJ rearrangement in DN cells. In contrast, once cells have progressed beyond the DN stage of development the IL-7R alpha chain becomes no longer essential for RAG expression.