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 deve lopment is arrested at the double-negative (DN) stage. We show that th ymocyte development in these mice can be reconstituted by the introduc tion of a transgenic T cell receptor (TCR), implying that one function of the IL-7R alpha chain is to initiate TCR gene rearrangement. Expre ssion of the recombinase-activating genes RAG1 and RAG2 was greatly re duced in the IL-7R alpha(-/-) thymuses, and in DN thymocytes from the TCR transgenic IL-7R alpha(-/-) mice, but was restored in double-posit ive thymocytes from the TCR transgenic IL-7R alpha(-/-) mice. These da ta suggest that the IL-7R alpha chain controls RAG expression and init iation of TCR beta chain VDJ rearrangement in DN cells. In contrast, o nce cells have progressed beyond the DN stage of development the IL-7R alpha chain becomes no longer essential for RAG expression.