View source for Interleukin 2

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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
 | image = IL2_Crystal_Structure.png
 | image_source = Human Interleukin 2 crystal structure

 | Name = Interleukin 2
 | HGNCid = 6001
 | Symbol = IL2
 | AltSymbols =; IL-2; TCGF; lymphokine
 | OMIM = 147680
 | ECnumber =  
 | Homologene = 488
 | MGIid = 96548
 | GeneAtlas_image1 = PBB_GE_IL2_207849_at_tn.png
 | Function = {{GNF_GO|id=GO:0005125 |text = cytokine activity}} {{GNF_GO|id=GO:0005134 |text = interleukin-2 receptor binding}} {{GNF_GO|id=GO:0019209 |text = kinase activator activity}} 
 | Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} 
 | Process = {{GNF_GO|id=GO:0006916 |text = anti-apoptosis}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0007155 |text = cell adhesion}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0019735 |text = antimicrobial humoral response}} {{GNF_GO|id=GO:0030101 |text = natural killer cell activation}} {{GNF_GO|id=GO:0030217 |text = T cell differentiation}} {{GNF_GO|id=GO:0030307 |text = positive regulation of cell growth}} 
 | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3558
    | Hs_Ensembl = ENSG00000109471
    | Hs_RefseqProtein = NP_000577
    | Hs_RefseqmRNA = NM_000586
    | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 123592080
    | Hs_GenLoc_end = 123597339
    | Hs_Uniprot = P60568
    | Mm_EntrezGene = 16183
    | Mm_Ensembl =  
    | Mm_RefseqmRNA = NM_008366
    | Mm_RefseqProtein = NP_032392
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr =  
    | Mm_GenLoc_start =  
    | Mm_GenLoc_end =  
    | Mm_Uniprot =  
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{{SI}}


==Overview==
'''Interleukin-2''' ('''IL-2''') is an [[interleukin]], a type of [[cytokine]] [[immune system]] signalling molecule, that is instrumental in the body's natural response to [[microbial]] [[infection]] and in discriminating between foreign (nonself) and self. IL-2 mediates its effects by binding to [[IL-2 receptor]]s, which are expressed by [[lymphocytes]], the cells that are responsible for immunity.

==Discovery and characterization==

The [[IL-2]] molecule was first characterized as a variably [[glycosylated]] 15,500 [[Atomic mass unit|Dalton]] protein capable of supporting long-term [[T lymphocyte]] (T cell) proliferation,<ref>{{cite journal | author=Robb R, Smith KA | title=Heterogeneity of human T-cell growth factor(s) due to variable glycosylation | date=1981 | journal=Mol. Immunol. | volume=18 | pages=1087-94 | pmid=6977702}}</ref> and was first purified to homogeneity by [[immunoaffinity chromatography]].<ref>{{cite journal | author=Smith KA, Favata MF, Oroszlan S | title=Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics | date=1983 | journal=J. Immunol. | volume=131 | pages=1808 | pmid=6352804}}</ref> The IL-2 molecule was also the first interleukin found to be encoded by a [[cDNA|complementary DNA]] (cDNA),<ref>{{cite journal | author=Taniguchi T, Matsui H, Fujita T, Takaoka C, Kashima N, Yoshimoto R, Hamuro J | title=Structure and expression of a cloned cDNA for human interleukin-2 | date=1983 |  journal=Nature. | volume=302 | issue=5906 | pages=305 | pmid=6403867}}</ref> and to mediate its effects via a specific [[IL-2 receptor]].<ref>{{cite journal | author=Robb RJ, Munck A, Smith KA | title=T cell growth factor receptors. Quantitation, specificity, and biological relevance  | date=1981 |journal=J. Exp. Med. |volume=154| issue=5| pages=1455-74 | pmid= 6975347}}</ref> 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 IL-1, produced by [[macrophages]], facilitates IL-2 production by T lymphocytes (T cells)<ref>{{cite journal | author=Smith KA, Lachman LB, Oppenheim JJ, Favata MF | date=1980 | title=The functional relationship of the interleukins  | journal=J. Exp. Med. | issue=6 | volume= 151 | pages=1551-6 | pmid=6770028}}</ref><ref>{{ cite journal | author=Smith KA, Gilbride KJ, Favata MF | title=Lymphocyte activating factor promotes T-cell growth factor production by cloned murine lymphoma cells |  date=1980 | journal=Nature. | volume=287  | issue=5785 | pages=853-5 | pmid=6776414 }}</ref>

==IL-2 signaling pathway==

Interleukin-2 belongs to a family of cytokines, which includes [[IL-4]], [[IL-7]], [[IL-9]], [[IL-15]] and [[IL-21]]. IL-2 signals through a receptor complex consisting of IL-2 specific IL-2 receptor alpha ([[CD25]]), IL-2 receptor beta ([[CD122]]) and a [[common gamma chain]] (γc), which is shared by all members of this family of cytokines. Binding of IL-2 activates the Ras/MAPK, JAK/Stat and PI 3-kinase/Akt signaling modules. More comprehensive details are provided in [http://www.netpath.org/pathways?path_id=NetPath_14 NetPath].

==Physiology and immunology==

IL-2 is normally produced by the body during an immune response.<ref>{{cite journal | author=Cantrell DA, Smith KA | title=The interleukin-2 T-cell system: a new cell growth model | date=1984 | journal= Science. | volume=224 | pages=1312-6 | pmid=6427923 }}</ref><ref>{{cite journal | author=Smith KA | title=Interleukin-2: inception, impact, and implications | date=1988 | journal=Science. | volume=240 | pages=1169-76 | pmid=3131876 }}</ref> 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 receptor ([[TCR]]) stimulates the secretion  of IL-2, and the expression of IL-2 receptors [[IL-2 receptor|IL-2R]]. The IL-2/IL-2R interaction then stimulates the growth, differentiation and survival of antigen-selected [[cytotoxic T cells]] via the activation of the expression of specific genes.<ref>{{cite journal | author=Stern J, Smith KA | title=Interleukin-2 induction of T-cell G1 progression and c-myb expression | date=1986 | journal=Science. |volume=233 | pages=203-6 | pmid=3523754 }}</ref><ref>{{cite journal | author=Beadling C, Johnson KW, Smith KA| date=1993 | title=Isolation of interleukin 2-induced immediate-early genes | journal=Proc. Nat. Acad. Sci. U.S.A. | volume=90 | pages=2719-23 | pmid=7681987 }}</ref><ref>}{{cite journal | author=Beadling CB, Smith KA | date=2002 | title=DNA array analysis of interleukin-2-regulated immediate/early genes | journal=Med. Immunol. | volume=1 | pages=2 | pmid=12459040 }}</ref> As such, IL-2 is necessary for the development 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.

IL-2 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).<ref>{{cite journal | author=Sakaguchi S,  Sakaguchi N, Asano M, Itoh M, Toda M | title=Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases | date=1995 | journal=J. Immunol. | volume=155 | pages=1151-64 | pmid=7636184 }}</ref><ref name="Thorton 1998">{{cite journal | author=Thornton AM, Shevach EM | title=CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production | date=1998 | journal=J. Exp. Med. | volume=188 | pages=287-96 | pmid=9670041 }}</ref><ref>{{cite journal | author=Thornton AM, Donovan EE, Piccirillo CA, Shevach EM | title=Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function | date=2004 | journal=J. Immunol. | volume=172 | pages=6519-23 | pmid=15153463 }}</ref> 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 IL-2<ref name="Thorton 1998"/> Thus, IL-2 is required to discriminate between self and non-self, another one of the unique characteristics of the immune system.

IL-2 has been found to be similar to [[interleukin-15|IL-15]] in terms of function.<ref name=Waldmann2006>{{cite journal | author=Waldmann TA | title=The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design | date=2006 | journal=Nature Rev. Immun. | volume=6 | issue=8 | pages=595-601 | pmid=16868550 }}</ref> Both cytokines are able to facilitate production of [[immunoglobulins]] made by [[B cells]] and induce the differentiation and proliferation of [[natural killer cells]].<ref name=Waldmann2006/><ref>{{cite journal | author=Waldmann TA, Tagaya Y | title=The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens | date=1999 | journal=Annu. Rev. Immunol.|volume=17 | pages=19-49 | pmid=10358752 }}</ref> The primary differences between IL-2 and [[interleukin-15|IL-15]] are found in [[adaptive immune system|adaptive immune]] responses. For example, IL-2 participates in maintenance of T-Regs and reduces self-reactive T cells. On the other hand, IL-15 is necessary for maintaining highly specific [[T cell]] responses by supporting survival of [[CD8]] [[memory T cells]]. The differences in function in these two cytokines stem from the [[signal transduction]] mechanisms and differing receptors.

==Uses in medicine==

A recombinant form of IL-2 is manufactured by [[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. The role of IL-2 in HIV therapy remains to be fully determined.

Many of the immunsuppressive drugs used in the treatment of autoimmune diseases such as [[corticosteroid]]s, and organ transplant rejection ([[cyclosporine]], [[tacrolimus]]) work by inhibiting the production of IL-2 by antigen-activated T cells. Others ([[Rapamycin]]) block IL-2R signaling, thereby preventing the clonal expansion and function of antigen-selected T cells.

==References==
{{reflist|2}}

==External links==

* [http://www.proleukin.com Proleukin website]
* [http://www.kendallasmith.us IL2 Resource Site]
* [http://www.netpath.org/pathways?path_id=NetPath_14 IL-2 Signaling Pathway]

{{interleukins}}

[[Category:Cytokines]]
[[Category:Cancer treatments]]

[[es:Interleucina-2]]
[[pl:Interleukina 2]]
[[sr:Интерлеукин 2]]
[[sv:Interleukin 2]]

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