| Interleukin‑2 (IL‑2) is a type I cytokine of the common γ‑chain family that is produced mainly by activated T cells and acts as a central regulator of T cell and NK cell expansion, differentiation, and survival. The protein adopts a four‑helix bundle fold typical of this cytokine family and signals through a receptor system composed of IL‑2Rα (CD25), IL‑2Rβ (CD122), and the common γ‑chain (γc, CD132), which assemble into receptors of different affinity depending on subunit composition and expression level on distinct lymphocyte subsets. IL‑2Rα binds IL‑2 with low affinity and presents the cytokine to IL‑2Rβ and γc, creating an intermediate‑ to high‑affinity signaling complex, whereas IL‑2Rβ and γc form the signaling core and are shared with other γc cytokines, with IL‑2Rβ also serving IL‑15 and γc participating in IL‑4, IL‑7, IL‑9, IL‑15, and IL‑21 receptor complexes. Engagement of IL‑2 with IL‑2Rβ and γc brings together the associated tyrosine kinases JAK1 and JAK3, induces their activation, and leads to phosphorylation of receptor cytoplasmic tails that recruit and activate STAT5, which dimerizes and translocates to the nucleus to drive transcription of IL‑2‑responsive genes. IL‑2 also connects to PI3K–Akt and MAPK pathways through docking of signaling intermediates on phosphorylated receptor motifs, generating additional outputs that influence metabolic activity, cell cycle progression, and survival in IL‑2‑responsive lymphocytes. Within CD4⁺ T cell populations, IL‑2–STAT5 signaling supports effector T cell proliferation and function and at the same time sustains regulatory T cell development, maintenance, and suppressive capacity, with Treg cells expressing high‑affinity IL‑2 receptors and depending on IL‑2 produced by conventional T cells. IL‑2 signaling contributes to activation‑induced cell death by promoting expression of death pathway components in expanded T cells and thereby participates in contraction of T cell responses after antigen clearance. Persistent or altered IL‑2 pathway activity associates with immune dysregulation, including autoimmunity when IL‑2 availability or IL‑2R signaling to Treg cells is reduced, and with impaired pathogen control or antitumor responses when effector IL‑2 responses are limited. |
