The lck promoter-driven expression of the Wilms tumor gene WT1 blocks intrathymic differentiation of T-lineage cells

In the thymi of WT1-transgenic (Tg) mice with the 17AA+/KTS- spliced form of the Wilms tumor gene WT1 driven by the Ick promoter, the frequencies of CD4(-)CD8(-) double-negative (DN) thymocytes were significantly increased relative to those in normal littermates. Of the 4 subsets of CD4(-)CD8(-) DN thymocytes, the DN1 (CD44(+)CD25(-)) subset increased in both frequency and absolute cell number, whereas the DN2 (CD44(+)CD25(+)) and DN3 (CD44(-)CD25(+)) subsets decreased, indicating the blocking of thymocyte differentiation from the DN1 to the DN2 subsets. Furthermore, CD4(-)CD8(+) T-cell receptor (TCR) gammadelta T-cells increased in both frequency and absolute cell number in the spleen and peripheral blood of the WT1-Tg mice relative to those of normal littermates. The CD8 molecules of these CD4(-)CD8(+) TCR gammadelta T-cells were CD8alphabeta, suggesting that they originated from the thymus. These results are the first direct evidence demonstrating that the WT1 gene is involved in the development and differentiation of T-lineage cells. (C)2003 The Japanese Society of Hematology.