Interleukin2

Interleukin-2 (IL-2) is a small cytokine produced primarily by activated CD4+ T cells, with lower levels produced by CD8+ T cells, natural killer cells, and dendritic cells. It acts as a key growth factor for T cells, promoting proliferation, survival, and differentiation in response to antigenic stimulation. IL-2 also supports the maintenance and function of regulatory T cells (Tregs), contributing to peripheral tolerance.

IL-2 exerts its effects by binding to the IL-2 receptor, which exists in three forms: a high-affinity trimer consisting of IL-2Rα (CD25), IL-2Rβ (CD122), and the common γ chain (IL-2Rγ); and intermediate affinity dimers lacking CD25. Binding activates intracellular signaling cascades, notably JAK-STAT (primarily JAK1 and JAK3 with STAT5), along with MAPK and PI3K pathways, leading to gene expression that supports T cell growth and survival.

Biological roles include expansion of activated T cells during immune responses, enhancement of natural killer (NK) cell cytotoxicity, and, via Tregs, modulation of immune tolerance. IL-2 production is tightly regulated by transcriptional and post-transcriptional mechanisms to balance immune activation and regulation.

Therapeutically, recombinant IL-2 (aldesleukin) has been approved for treatment of certain cancers, including metastatic renal cell carcinoma and metastatic melanoma, though its use can produce significant toxicity, such as capillary leak syndrome, hypotension, and organ dysfunction. IL-2 therapies exploit its capacity to boost anti-tumor T cell responses, but dosing and patient selection are critical. Research continues into low-dose regimens to favor Treg expansion in autoimmune diseases and transplantation tolerance.

IL-2 remains a central cytokine in immunology, illustrating the balance between immune activation and regulation. Owing to its pleiotropic actions, IL-2 is a common target in therapeutic strategies aiming to modulate T cell responses in cancer, autoimmunity, and transplantation.