Article: Interleukin 2

Interleukin-2 (IL2) is an interleukin, or hormone of the immune system that is instrumental in the body's natural response to microbial infection and in discriminating between foreign (nonself) and self. IL2 mediates its effects by binding to IL2 receptors, which are expressed by lymphocytes, the cells that are responsible for immunity.

Discovery and Characterization

The IL2 molecule was first characterized as a variably glycosylated 15,500 Dalton protein capable of supporting long-term T lymphocyte (T cell) proliferation (Robb, R. & Smith,K.A. 1981), and was first purified to homogeneity by immunoaffinity chromatography (Smith, K.A., et. al., 1983). The IL2 molecule was also the first interleukin found to be encoded by a complimentary DNA (cDNA)(Taniguchi, T. et. al. 1983), and to mediate its effects via specific IL2 receptors (Robb, R. et. al., 1981). Thus, despite being designated the number 2 interleukin, it was the first interleukin molecule, gene and receptor to be discovered. It was designated number 2 because data at the time indicated that IL1, produced by macrophages, facilitates IL2 production by T lymphocytes (T cells) (Smith, K.A., et.al. 1980).

Physiology & Immunology

IL2 is normally produced by the body during an immune response (Cantrell, D.A. & Smith, K.A. 1984; Smith, K.A. 1988). When environmental substances (molecules or microbes) gain access to the body, these substances (termed antigens) are recognized as foreign by antigen receptors that are expressed on the surface of lymphocytes. Antigen binding to the T Cell antigen Receptors (TCR) stimulates the secretion of IL2, and the expression of IL2 receptors IL2R. The IL2/IL2R interaction then stimulates the growth, differentiation and survival of antigen-selected T cells via the activation of the expression of specific genes (Stern, J & Smith, K.A. 1986; Beadling, et.al. 1993; Beadling , C. & Smith, K.A. 2002). As such, IL2 is necessary for the develpoment of T cell immunologic memory, one of the unique characteristics of the immune system, which depends upon the expansion of the number and function of antigen-selected T cell clones.

IL2 is also necessary during T cell development in the thymus for the maturation of a unique subset of T cells that are termed Regulatory T cells (T-Regs)(Sakaguchi, S. et.al. 1995; Thorton, A.M. & Shevach, E. 1998; Thorton, A.M. et. al. 2004). After exiting from the thymus, T-Regs function to prevent other T cells from recognizing and reacting against "self antigens", which could result in "autoimmunity". T-Regs do so by preventing the responding cells from producing IL2 (Thornton A.M. & Shevach, E. 1998). Thus, IL2 is required to discriminate between self and non-self, another one of the unique characteristics of the immmue system.

Uses in Medicine

A recombinant form of IL2 is manufactured by the Chiron Corporation with the brand name Proleukin. It has been approved by the Food and Drug Administration (FDA) for the treatment of cancers (malignant melanoma, renal cell cancer), and is in clinical trials for the treatment of chronic viral infections, and as a booster (adjuvant) for vaccines.

Many of the immunsuppressive drugs used in the treatmant of autoimmune diseases such as corticosteroids, and organ transplant rejection (Cyclosporin-A, Tacrolimus) work by inhibiting the production of IL2 by antigen-activated T cells. Others (Rapamycin) block IL2R signaling, thereby preventing the clonal expansion and function of antigen-selected T cells.