Biology and regulation of IL-2: from molecular mechanisms to human therapy

IL-2 was first identified as a growth factor capable of driving the expansion of activated human T cell populations. In the more than 40 years since its discovery, a tremendous amount has been learned regarding the mechanisms that regulate the expression of both IL-2 and its cell surface receptor, its mechanisms of signalling and its range of biological actions. More recently, the mechanisms by which IL-2 regulates CD4⁺ T cell differentiation and function have been elucidated. IL-2 also regulates the effector and memory responses of CD8⁺ T cells, and the loss of IL-2 or responsiveness to IL-2 at least in part explains the exhausted phenotype that occurs during chronic viral infections and in tumour responses. These basic mechanistic studies have led to the therapeutic ability to manipulate the action of IL-2 on regulatory T (T_reg) cells for the treatment of autoimmune disease and on CD8⁺ T cells for immunotherapy of cancer. IL-2 can have either positive or deleterious effects, and we discuss here recent ideas and approaches for manipulating the actions and overall net effects of IL-2 in disease settings, including cancer.