The Lasting Impact of IL-2: Approaching 50 Years of Advancing Immune Tolerance, Cancer Immunotherapies, and Autoimmune Diseases

BACKGROUND: The discovery of interleukin-2 (IL-2) and its receptor (IL-2R) almost 50 years ago revolutionized immunology, marking a pivotal moment in understanding T cell biology and immune regulation. Initially identified as a T cell growth factor, IL-2 unveiled critical insights into cytokine-mediated immune cell proliferation and differentiation. METHODS: This review highlighted the characterization of IL-2R as a multi-chain receptor complex set a precedent for decoding cytokine receptor signaling. The unique interplay between IL-2 and its high-affinity receptor component, IL-2Rα, epitomizes the principle of specificity and efficiency in cytokine signaling, enabling precise immune modulation. Regulatory T cells (Tregs) exploit IL-2Rα high affinity to outcompete effector T cells for IL-2, ensuring immune tolerance and preventing autoimmunity. RESULTS: Despite its foundational role in immune homeostasis, leveraging IL-2 for therapeutic purposes has proven challenging. CONCLUSION: IL-2-based therapies hold transformative potential in autoimmunity, cancer immunology, and transplantation, yet they remain elusive due to the complex balance between immunostimulatory and immunosuppressive effects. This review explores the milestones in IL-2 biology, its dualistic functions, and the ongoing quest to harness its therapeutic promise.