Defective development of gamma/delta T cells in interleukin 7 receptor-deficient mice is due to impaired expression of T cell receptor gamma genes

Mice lacking the interleukin 7 receptor (IL-7R) generate alpha/beta T cells at a detectable but greatly reduced rate, but gamma/delta T cells are comp letely absent. The special role of IL-7R signaling in gamma/delta T cell de velopment has remained unclear. IL-7R alpha(-/-) mice exhibit a paucity of gamma gene rearrangements. This striking observation can be explained by a defect in T cell receptor (TCR)-gamma gene rearrangement, a defect in TCR-g amma gene transcription leading to death of gamma/delta lineage cells, and/ or a requirement for IL-7R in commitment of cells to the gamma/delta lineag e. To determine the role of IL-7R signaling in gamma/delta T cell developme nt, we examined transcription of a prerearranged TCR-gamma transgene in IL- 7R alpha(-/-) mice, as well as the effects of IL-7 on transcription of endo genous, rearranged TCR-gamma genes in alpha/beta lineage cells. The results demonstrate that IL-7R-mediated signals are necessary for the normal expre ssion of rearranged TCR-gamma genes. Equally significant, the results show that the poor expression of TCR-gamma genes in IL-7R alpha(-/-) mice is res ponsible for the selective deficit in gamma/delta cells in these mice, sinc e a high copy TCR-gamma transgene exhibited sufficient residual expression in IL-7R alpha(-/-) mice to drive gamma/delta cell development. The results indicate that the absence of gamma/delta T cells in IL-7R alpha(-/-) mice is due to insufficient TCR-gamma gene expression.