The role of interleukin-7 in early T-cell development

Interleukin-7 (IL-7) is a non redundant cytokine in thymic T-cell development. It binds to a dimeric receptor consisting of a specific IL-7Ralpha and a gamma-common subunit that it shares with the receptors for IL-2, 4, 9, 13 and 15. IL-7 is critical for early T-cell development but it also acts on immature B-cells and mature T-cells, and leads to secondary cytokine release. Its mechanisms of action in early T-cell development may be multiple. There is direct evidence to support a mechanistic involvement in TCR-gamma rearrangement that drives further TCR-gammadelta thymocyte commitment and maturation. There is indirect evidence for a role of IL-7 in TCR-beta rearrangement. It may however also act as a survival factor for TCR-beta rearranging thymocytes while the critical commitment selections are effected by other factors. The effects of IL-7 in fetal thymus organ culture are dose dependent, with a biphasic response: low doses of IL-7 are necessary for normal TCR-alphabeta thymocyte development but high doses block TCR-alphabeta maturation in favor of TCR-gammadelta development. A good understanding of the dose response of IL-7 in thymocyte development, mature T-cell stimulation, and of the release of secondary cytokines will be important for planning successful clinical trials with IL-7.