IL-7 downregulates IL-7Rα expression in human CD8 T cells by two independent mechanisms

Interleukin (IL)-7 is an essential nonredundant cytokine, and throughout the lifespan of a T-cell signaling via the IL-7 receptor influences cell survival, proliferation and differentiation. It is therefore no surprise that expression of the IL-7 receptor alpha-chain (CD127) is tightly regulated. We have previously shown that IL-7 downregulates expression of CD127 at the cell surface and now elucidate the kinetics of that suppression and demonstrate that IL-7 downregulates CD127 transcripts and surface protein in primary human CD8 T cells by two separate pathways. We show that IL-7 induces the initial reduction in cell-surface CD127 protein independent of transcriptional suppression, which is delayed by 40-60 min. Although IL-7-mediated downregulation of CD127 transcripts is dependent on Janus kinase (JAK)/STAT5, the early downregulation of surface CD127 protein is independent of JAK activity. The data further illustrate that low levels of IL-7 induce smaller and transient decreases in CD127 transcripts and surface protein, whereas higher concentrations induce more profound and sustained suppression. Such flexibility in receptor expression likely allows for fine-tuned immune responses in human CD8 T cells in different microenvironments and in response to different immunological challenges.