DEFECTIVE T-CELL RECEPTOR-GAMMA GENE REARRANGEMENT IN INTERLEUKIN-7 RECEPTOR KNOCKOUT MICE

T-cell receptor (TCR) genes need to be rearranged by a site specific-V DJ recombinase before they are expressed. This process, initiated in C D44(+)25(+) thymocytes, takes place during the early stages of T-cell differentiation in the thymus. Interleukin-7 receptor a chain knockout (IL-7R(-/-)) mice are severely deficient in B-lymphocytes and alpha b eta T-cells and completely lack the gamma delta T-cell lineage. Thymoc yte development is arrested at a very early stage (DN CD44(+)CD25(-)). Because this arrest is earlier than in mice with a block in VDJ recom bination, we examined the rearrangement status of TCR genes in thymocy tes from IL-7R(-/-) mice. The TCR beta locus showed a nearly normal pa ttern of VDJ rearrangements, consistent with the presence of alpha bet a T-cells in these mice. However, TCR gamma locus rearrangement was ab sent or severely reduced for all the V gamma genes analyzed (V gamma 3 , V gamma 4, V gamma 1.1, V gamma 1.2 and V gamma 2). In contrast, the delta locus showed little reduction in rearrangement. The defect in g amma rearrangements in IL-7R(-/-) thymocytes is not simply due to an a bsence of mature gamma delta T-cells, since TCR delta(-/-) mice, which also have only alpha beta T-cells, had normal levels of gamma and del ta rearrangements. These findings indicate that one or both of the two known ligands of IL-7R, IL-7 and thymic stromal lymphopoietin (TSLP) serves as an extrinsic signal to specifically rearrange the TCR gamma locus. (C) 1997 Elsevier Science B.V.