Cell biology of IL-7, a key lymphotrophin

IL-7 is essential for the development and survival of T lymphocytes. This review is primarily from the perspective of the cell biology of the responding T cell. Beginning with IL-7 receptor structure and regulation, the major signaling pathways appear to be via PI3K and Stat5, although the requirement for either has yet to be verified by published knockout experiments. The proliferation pathway induced by IL-7 differs from conventional growth factors and is primarily through posttranslational regulation of p27, a Cdk inhibitor, and Cdc25a, a Cdk-activating phosphatase. The survival function of IL-7 is largely through maintaining a favorable balance of bcl-2 family members including Bcl-2 itself and Mcl-1 on the positive side, and Bax, Bad and Bim on the negative side. There are also some remarkable metabolic effects of IL-7 withdrawal. Studies of IL-7 receptor signaling have yet to turn up unique pathways, despite the unique requirement for IL-7 in T cell biology. There remain significant questions regarding IL-7 production and the major producing cells have yet to be fully characterized.