Defective Development of γ/δ T Cells in Interleukin 7 Receptor–Deficient Mice Is Due to Impaired Expression of T Cell Receptor γ Genes

Mice lacking the interleukin 7 receptor (IL-7R) generate α/β T cells at a detectable but greatly reduced rate, but γ/δ T cells are completely absent. The special role of IL-7R signaling in γ/δ T cell development has remained unclear. IL-7Rα(−/−) mice exhibit a paucity of γ gene rearrangements. This striking observation can be explained by a defect in T cell receptor (TCR)-γ gene rearrangement, a defect in TCR-γ gene transcription leading to death of γ/δ lineage cells, and/or a requirement for IL-7R in commitment of cells to the γ/δ lineage. To determine the role of IL-7R signaling in γ/δ T cell development, we examined transcription of a prerearranged TCR-γ transgene in IL-7Rα(−/−) mice, as well as the effects of IL-7 on transcription of endogenous, rearranged TCR-γ genes in α/β lineage cells. The results demonstrate that IL-7R–mediated signals are necessary for the normal expression of rearranged TCR-γ genes. Equally significant, the results show that the poor expression of TCR-γ genes in IL-7Rα(−/−) mice is responsible for the selective deficit in γ/δ cells in these mice, since a high copy TCR-γ transgene exhibited sufficient residual expression in IL-7Rα(−/−) mice to drive γ/δ cell development. The results indicate that the absence of γ/δ T cells in IL-7Rα(−/−) mice is due to insufficient TCR-γ gene expression.