The Role of Interleukin-7 in Early T-Cell Development

Abstract

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-7Rα and a γ-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-γ rearrangement that drives further TCR-γδ thymocyte commitment and maturation. There is indirect evidence for a role of IL-7 in TCR-β rearrangement. It may however also act as a survival factor for TCR-β 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-αβ thymocyte development but high doses block TCR-αβ maturation in favor of TCR-γδ 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.

Key Words:

• Interleukin 7
• early T-cells