IL-2 Signaling Pathways and their Primary Biological Effects in Different Immune Cell Types

Interleukin-2 (IL-2) is an O-glycosylated four alpha-helix bundle cytokine that is primarily produced by activated T cells, dendritic cells, and B cells. The biological activity of IL-2 is mediated by binding to a cell surface receptor complex consisting of IL-2 R alpha/CD25, IL-2/IL-15 R beta, and the common gamma-chain/IL-2 R gamma subunit. IL-2 can also bind with low affinity to IL-2 R alpha alone, or with intermediate affinity to a complex consisting of IL-2/IL-15 R beta and the common gamma-chain subunit. Functionally, IL-2 induces the expression of both IL-2 and IL-2 R alpha on activated CD4⁺ and CD8⁺ T cells and stimulates their proliferation. In contrast, IL-2 also plays an important role in the maintenance of peripheral self-tolerance both by initiating Fas-mediated activation-induced cell death of CD4⁺ T cells following antigen restimulation and by its ability to promote the differentiation and survival of regulatory T cells. Rather than displaying a severe immunodeficient phenotype, mice lacking IL-2, IL-2 R alpha, or IL-2 R beta accumulate activated T lymphocytes, have reduced numbers of regulatory T cells, and develop autoimmune diseases. This suggests that the maintenance of T cell homeostasis and prevention of self-reactivity is the primary function of IL-2 signaling. In addition, IL-2 may enhance the cytotoxicity of natural killer cells and may be required for B cell proliferation and immunoglobulin production.

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