Interleukin-2 (IL2) was initially identified from supernatants of activated lymphocytes over 30 years ago. In the ensuing 15 years, the cDNAs for both IL2 and the three chains of the interleukin-2 receptor (IL2R) were cloned. Subsequently, many of the downstream biochemical pathways activated by the IL2 receptor complex were identified and the structure of IL2 bound to this tripartite receptor complex was solved. Thus, we now have a very good understanding of how each chain contributes to high affinity IL2 binding and signal transduction. In contrast, over the past 30 years the role that IL2 plays in regulating lymphocyte function has involved many surprising twists and turns. For example, IL2 has been shown, paradoxically, to regulate both lymphocyte proliferation and lymphocyte death. In this review, we briefly outline the original findings suggesting a role for IL2 as a T cell growth factor, as well as subsequent studies pointing to its function as an initiator of activation-induced cell death, but then focus on the newly appreciated role for IL2 and IL2R signaling in the development and homeostasis of regulatory T cells.
Bibliographical noteFunding Information:
This work was supported by grants from the NIH (AI061165) and by a Pew Scholar Award, a Cancer Research Investigator Award and a Leukemia and Lymphoma Society Scholar Award to M.A.F. M.A.B. was supported by an NIH training grant (2T32-AI07313).
- Regulatory T cell
- Signal transduction