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Abstract
IL-2 is a four-helix bundle cytokine that was initially identified as a T cell growth factor more than two decades ago. Since then, extensive investigations have led to the discovery of additional cytokines, including IL-4, IL-7, IL-9, IL-15 and IL-21, which display many similarities with IL-2 and have been grouped, together with the latter, as a distinct IL-2 cytokine family. These cytokines are all globular proteins that contain two sets of short-chain α-helical domains. They all play major roles in promoting and maintaining T lymphocyte populations, albeit in non-redundant and often complementary manners, whilst acting on other cell lineages as well. Most remarkably, their cell surface receptor complexes, which consist of two or three subunits, including a cytokine-specific private subunit, all use a shared subunit called the common γ chain (γc). This common subunit was shown to be mutated in X-linked severe combined immunodeficiency and to uniquely recruit the Janus kinase, Jak3. Accordingly, IL-2 family cytokines all utilise Jak3 in their mechanisms of intracellular signalling, together with more ubiquitous kinases. Owing to their prominent roles in lymphocyte development and homeostasis, IL-2 family cytokines have been the focus of much interest for the purpose of therapeutic applications. They may provide tools to bolster immune responses for the treatment of neoplastic diseases, viral infections and immunodeficiencies. Conversely, their blockade may help achieve immunosuppression for the treatment of transplant rejection, as well as inflammatory, autoimmune and allergic disorders. Here, the patent literature of the past four years pertaining to these important cytokines will be reviewed in the context of the current understanding of their biological significance.