The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, prolifeRation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis.
Interleukin-2 (IL-2) is a O-glycosylated, four alpha -helix bundle cytokine that has potent stimulatory activity for antigen-activated T cells. It is expressed by CD4+ and CD8+ T cells, gamma δ T cells, B cells, dendritic cells, and eosinophils. Mature human IL-2 shares 56% and 66% aa sequence identity with Mouse and Rat IL-2, respectively. Human and Mouse IL-2 exhibit cross-species activity. The receptor for IL-2 consists of three subunits that are present on the cell surface in varying preformed complexes. The 55 kDa IL-2 R alpha is specific for IL-2 and binds with low affinity. The 75 kDa IL-2 R beta, which is also a component of the IL-15 receptor, binds IL-2 with intermediate affinity. The 64 kDa common gamma chain gamma c/IL-2 R gamma, which is shared with the receptors for IL-4, -7, -9, -15, and -21, does not independently interact with IL-2. Upon ligand binding, signal transduction is performed by both IL-2 R beta and gamma c. IL-2 is best known for its autocrine and paracrine activity on T cells. It drives resting T cells to prolifeRate and induces IL-2 and IL-2 R alpha synthesis. It contributes to T cell homeostasis by promoting the Fas-induced death of naïve CD4+ T cells but not activated CD4+ memory lymphocytes. IL-2 plays a central role in the expansion and maintenance of regulatory T cells, although it inhibits the development of Th17 polarized cells. Thus, IL-2 may be a key cytokine in the natural suppression of autoimmunity.
IL-4 is a pleiotropic cytokine that is produced by activated T cells, mast cells, and basophils. IL-4 elicits many different biological responses but has two dominant functions. The first is regulating differentiation of naive CD4+ T cell to the Th2 type. Th2 cells produce IL-4, IL-5, IL-10, and IL-13, which tend to favor a humoral immune response while suppressing a cell-mediated immune response controlled by Th1 cells. The second is regulating IgE and IgG1 production by B cells.
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