The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Il2  -  interleukin 2

Mus musculus

Synonyms: IL-2, Il-2, Interleukin-2, T-cell growth factor, TCGF
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Il2


Psychiatry related information on Il2


High impact information on Il2

  • High concentrations of antigen (or anti-TCR mAb) inhibit IL-2-induced proliferation (but not lymphokine production) by TH1 and cytolytic T lymphocyte (CTL) clones only [12].
  • The general impression is that CD8+ cytotoxic T lymphocytes, CD4+ TH1 cells, gamma interferon, and IL-2 are of major importance, with these different components of the immune system interacting to promote an optimal response [13].
  • QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2 [14].
  • Four QTLs Cinda (Cytokine induced activation) loci that control activation of splenocytes by IL-2 and/or IL-4 [15] [16] have been found to be genetically linked with the lung cancer susceptibility [17]. Moreover the independently detected susceptibility loci for proteoglycan-induced arthritis map within 1 cM of three out of the four Sluc loci that co-localize with Cinda loci: Cinda4-Sluc1-Pgia12, Cinda1-Sluc4-Pgia7, and Cinda5-Sluc20-Pgia4 [18][15] [16] [17]. The possible basis of relationship between genetic control of cytokine responsiveness, tumour and autoimmunity susceptibility may be also due to common signalling pathways stimulated by IL-2 and/or IL-4 in lymphocytes and in tumor cells.
  • Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation [19].
  • By this approach, two retroviral producer cell lines encoding cytokines (IL-4 and IL-2) directed tumoricidal inflammatory responses to established metastases [20].

Chemical compound and disease context of Il2


Biological context of Il2

  • We report here the mapping of Aod2, the locus that controls this phenotype, to mouse chromosomes 3 within a region encoding Il2 and Fgfb [26].
  • To investigate whether sequence variation exists in the promoter region of the Il2 gene, which might alter its expression, we sequenced the promoter region of the Il2 gene from mouse strains carrying either an Idd3 susceptibility or resistance allele [27].
  • During Ag stimulation of T cells, the recognition of B7 molecules by the CD28 costimulatory receptor increases the level of c-Fos, a component of the AP-1 transactivator known to bind the 5' Il2 gene enhancer [28].
  • Using this approach, we localized the Idd3 locus to a 0.35-cM interval on chromosome 3 containing the Il2 gene [29].
  • These data, taken together with the immunomodulatory role of IL-2, provide circumstantial evidence in support of the hypothesis that Idd3 is an allelic variation of the Il2 gene, or a variant in strong linkage disequilibrium [29].

Anatomical context of Il2

  • Unexpectedly, Il2(-/-) and Il2ra(-/-) T(reg) cells were fully able to suppress T cell proliferation in vitro [30].
  • This is in contrast to the known requirement for IL-2 in NK cell growth [31].
  • More recently, there has been evidence for the involvement of IL-2 per se in the stimulation of B-cell growth (ref. 10 and T. Kishimoto and J. Vilcek, personal communications) [32].
  • Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling [33].
  • Treatments of euthymic mice with high-dose IL-2 also induced transcription of the alpha chain gene in 41% of the non-B blast lymphocytes, but only background percentages of the NK1.1+ cells expressed the alpha chain gene [34].

Associations of Il2 with chemical compounds


Physical interactions of Il2

  • Proteins with bulky or basic substitutions at residue D34 were weak antagonists due to severely reduced IL-2 binding and their reduced binding paralleled their defects in IL-2R activation [38].
  • IL-2 induced the binding of Stat5a and b proteins to the human GASd element [39].
  • Binding data and Scatchard analysis support these results and show an increase from 3100 to 17,620 low-affinity IL-2 binding sites per cell without any change in affinity after induction of M1 cells by the combination of IL-6 and IL-1 [40].
  • The results presented demonstrate that IL-2 signal transduction results in the functional uncoupling of the TCR complex through altering the subcellular distribution of kinase-active Lck [41].
  • The amino terminus of JAK3 is necessary and sufficient for binding to the common gamma chain and confers the ability to transmit interleukin 2-mediated signals [42].

Enzymatic interactions of Il2


Regulatory relationships of Il2

  • Nuclear factor of activated T cells (NFAT) is a transcription factor that regulates expression of the cytokine interleukin-2 (IL-2) in activated T cells [45].
  • Exogenous recombinant (r)IL-2 only partially reverses NOD thymocyte proliferative unresponsiveness to anti-CD3, and this is mediated by the inability of IL-2 to stimulate a complete IL-4 secretion response [46].
  • In contrast, recombinant IL-2 induced IL-5 mRNA expression but did not induce detectable expression of IL-4 or granulocyte-macrophage colony-stimulating factor mRNA [47].
  • The combination of IL-18 plus IL-2 or IL-12 up-regulates IFN-gamma gene expression and NK cytotoxicity and has synergistic antitumor activity in vivo and in vitro [48].
  • Stem cell factor enhances interleukin-2-mediated expansion of murine natural killer cells in vivo [49].
  • Our study demonstrated a novel role of IL-2 in regulating multiorgan autoimmune inflammation beyond the Treg checkpoint and indicated that both Il2-/- and Faslpr/lpr genes prolong the lifespan of Sf mice but by different mechanisms [50].

Other interactions of Il2

  • Interestingly, the two lymphokines differed in that IL-2, but not BSF-1, induced a lytic population in cultures of unprimed cells without an overt antigenic stimulus [51].
  • IL-15 and IL-2: a matter of life and death for T cells in vivo [52].
  • In response to mitogenic signals, peripheral T cells in Jak3-deficient mice did not proliferate and secreted small amounts of IL-2 [53].
  • Interestingly, the cytokines IL-2 and IFN gamma were minimally affected [54].
  • Correspondingly, Stat5a-/- splenocytes exhibited markedly decreased proliferation to IL-2, although maximal proliferation was still achieved at IL-2 concentrations high enough to titrate intermediate-affinity IL-2R beta/gamma(c) receptors [55].

Analytical, diagnostic and therapeutic context of Il2

  • Because so much of the work on IL-2 has been done in the human and mouse, we sought to obtain cDNA encoding murine IL-2, and we now report the cloning, expression and sequence analysis of murine IL-2 cDNAs [32].
  • IL-2, IL-4, and tumor necrosis factor beta (IFN beta) comprised the third group and these cytokines were expressed only in allogeneic grafts after transplantation [56].
  • Flow cytometry indicated that TPA and its related phorbol esters cause a perturbation in the cycling of the cell which may be related to increased IL-2 production [5].
  • Vaccination with B16 cells producing IL-4 or gamma-interferon had no effect, and vaccination with B16 cells producing IL-2 decreased survival time [57].
  • This activity, herein designated B-cell growth factor (BCGF), has a Mr of approximately equal to 20,000 and it can readily be separated from TCGF (Mr approximately equal to 30,000) by gel filtration [37].




















  1. Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expressing v-myc oncogenes. Rapp, U.R., Cleveland, J.L., Brightman, K., Scott, A., Ihle, J.N. Nature (1985) [Pubmed]
  2. Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis. Lenardo, M.J. Nature (1991) [Pubmed]
  3. Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. Kondo, M., Takeshita, T., Higuchi, M., Nakamura, M., Sudo, T., Nishikawa, S., Sugamura, K. Science (1994) [Pubmed]
  4. Interferon gamma is involved in the recovery of athymic nude mice from recombinant vaccinia virus/interleukin 2 infection. Karupiah, G., Blanden, R.V., Ramshaw, I.A. J. Exp. Med. (1990) [Pubmed]
  5. Multiple lymphokine production by a phorbol ester-stimulated mouse thymoma: relationship to cell cycle events. Pearlstein, K.T., Staiano-Coico, L., Miller, R.A., Pelus, L.M., Kirch, M.E., Stutman, O., Palladino, M.A. J. Natl. Cancer Inst. (1983) [Pubmed]
  6. Interleukin-2 activates the gamma-interferon gene in newborn mice. Lipoldová, M., Holán, V. Immunol. Cell. Biol. (1991) [Pubmed]
  7. Influence of acute and repeated interleukin-2 administration on spatial learning, locomotor activity, exploratory behaviors, and anxiety. Lacosta, S., Merali, Z., Anisman, H. Behav. Neurosci. (1999) [Pubmed]
  8. Anti-TNF-alpha antibody normalizes serum leptin in IL-2 deficient mice. Gaetke, L.M., Oz, H.S., Frederich, R.C., McClain, C.J. Journal of the American College of Nutrition. (2003) [Pubmed]
  9. Different effects of IL-2 in vivo treatment and emotional stress on POMC gene expression in the pituitary of mice. Chesnokova, V., Busick, J., Chesnokov, V., Jakobson, G., Ivanova, L. Horm. Metab. Res. (1997) [Pubmed]
  10. Influence of chronic interleukin-2 infusion and stressors on sickness behaviors and neurochemical change in mice. Sudom, K., Turrin, N.P., Hayley, S., Anisman, H. Neuroimmunomodulation (2004) [Pubmed]
  11. Treatment of mice bearing BCL1 lymphoma with bispecific antibodies. Brissinck, J., Demanet, C., Moser, M., Leo, O., Thielemans, K. J. Immunol. (1991) [Pubmed]
  12. Differential regulation of murine T lymphocyte subsets. Fitch, F.W., McKisic, M.D., Lancki, D.W., Gajewski, T.F. Annu. Rev. Immunol. (1993) [Pubmed]
  13. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Doherty, P.C., Allan, W., Eichelberger, M., Carding, S.R. Annu. Rev. Immunol. (1992) [Pubmed]
  14. QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2. Encinas, J.A., Wicker, L.S., Peterson, L.B., Mukasa, A., Teuscher, C., Sobel, R., Weiner, H.L., Seidman, C.E., Seidman, J.G., Kuchroo, V.K. Nat. Genet. (1999) [Pubmed]
  15. IL-2-induced proliferative response is controlled by loci Cinda1 and Cinda2 on mouse chromosomes 11 and 12: a distinct control of the response induced by different IL-2 concentrations. Krulová, M., Havelková, H., Kosarová, M., Holán, V., Hart, A.A., Demant, P., Lipoldová, M. Genomics. (1997) [Pubmed]
  16. Novel loci controlling lymphocyte proliferative response to cytokines and their clustering with loci controlling autoimmune reactions, macrophage function and lung tumor susceptibility. Lipoldová, M., Havelková, H., Badalová, J., Demant, P. Int. J. Cancer. (2005) [Pubmed]
  17. Complexity of lung cancer modifiers: mapping of thirty genes and twenty-five interactions in half of the mouse genome. Tripodis, N., Hart, A.A., Fijneman, R.J., Demant, P. J. Natl. Cancer. Inst. (2001) [Pubmed]
  18. Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis. Otto, J.M., Cs-Szabó, G., Gallagher, J., Velins, S., Mikecz, K., Buzás, E.I., Enders, J.T., Li, Y., Olsen, B.R., Glant, T.T. Arthritis. Rheum. (1999) [Pubmed]
  19. Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation. Miyazaki, T., Liu, Z.J., Kawahara, A., Minami, Y., Yamada, K., Tsujimoto, Y., Barsoumian, E.L., Permutter, R.M., Taniguchi, T. Cell (1995) [Pubmed]
  20. Gene therapy of metastatic cancer by in vivo retroviral gene targeting. Hurford, R.K., Dranoff, G., Mulligan, R.C., Tepper, R.I. Nat. Genet. (1995) [Pubmed]
  21. T-cell-replacing factor (interleukin 5) induces expression of interleukin 2 receptors on murine splenic B cells. Loughnan, M.S., Takatsu, K., Harada, N., Nossal, G.J. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  22. Bacillus Calmette-Guérin plus interleukin-2 and/or granulocyte/macrophage-colony-stimulating factor enhances immunocompetent cell production of interferon-gamma, which inhibits B16F10 melanoma cell growth in vitro. Fujimoto, T., O'Donnell, M.A., Szilvasi, A., Yang, H., Duda, R.B. Cancer Immunol. Immunother. (1996) [Pubmed]
  23. Evaluation of combined vaccinia virus-mediated antitumor gene therapy with p53, IL-2, and IL-12 in a glioma model. Chen, B., Timiryasova, T.M., Andres, M.L., Kajioka, E.H., Dutta-Roy, R., Gridley, D.S., Fodor, I. Cancer Gene Ther. (2000) [Pubmed]
  24. Comparison of phage pVIII and KLH as vector in inducing the production of cytokines in C57BL/6J mice. Su, Q.P., Wen, D.Z., Yang, Q., Zhang, Y.H., Liu, C., Wang, L. Vaccine (2007) [Pubmed]
  25. Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2. Mocchegiani, E., Perissin, L., Santarelli, L., Tibaldi, A., Zorzet, S., Rapozzi, V., Giacconi, R., Bulian, D., Giraldi, T. Int. J. Immunopharmacol. (1999) [Pubmed]
  26. Aod2, the locus controlling development of atrophy in neonatal thymectomy-induced autoimmune ovarian dysgenesis, co-localizes with Il2, Fgfb, and Idd3. Teuscher, C., Wardell, B.B., Lunceford, J.K., Michael, S.D., Tung, K.S. J. Exp. Med. (1996) [Pubmed]
  27. Congenic mapping of the type 1 diabetes locus, Idd3, to a 780-kb region of mouse chromosome 3: identification of a candidate segment of ancestral DNA by haplotype mapping. Lyons, P.A., Armitage, N., Argentina, F., Denny, P., Hill, N.J., Lord, C.J., Wilusz, M.B., Peterson, L.B., Wicker, L.S., Todd, J.A. Genome Res. (2000) [Pubmed]
  28. p300/Cyclic AMP-responsive element binding-binding protein mediates transcriptional coactivation by the CD28 T cell costimulatory receptor. Nandiwada, S.L., Li, W., Zhang, R., Mueller, D.L. J. Immunol. (2006) [Pubmed]
  29. Mapping of the IDDM locus Idd3 to a 0.35-cM interval containing the interleukin-2 gene. Denny, P., Lord, C.J., Hill, N.J., Goy, J.V., Levy, E.R., Podolin, P.L., Peterson, L.B., Wicker, L.S., Todd, J.A., Lyons, P.A. Diabetes (1997) [Pubmed]
  30. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Fontenot, J.D., Rasmussen, J.P., Gavin, M.A., Rudensky, A.Y. Nat. Immunol. (2005) [Pubmed]
  31. Selective growth of natural cytotoxic but not natural killer effector cells in interleukin-3. Djeu, J.Y., Lanza, E., Pastore, S., Hapel, A.J. Nature (1983) [Pubmed]
  32. Unique structure of murine interleukin-2 as deduced from cloned cDNAs. Kashima, N., Nishi-Takaoka, C., Fujita, T., Taki, S., Yamada, G., Hamuro, J., Taniguchi, T. Nature (1985) [Pubmed]
  33. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. D'Cruz, L.M., Klein, L. Nat. Immunol. (2005) [Pubmed]
  34. Interleukin 2-induced proliferation of murine natural killer cells in vivo. Biron, C.A., Young, H.A., Kasaian, M.T. J. Exp. Med. (1990) [Pubmed]
  35. Retinoids are important cofactors in T cell activation. Garbe, A., Buck, J., Hämmerling, U. J. Exp. Med. (1992) [Pubmed]
  36. Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction. Kobayashi, N., Kono, T., Hatakeyama, M., Minami, Y., Miyazaki, T., Perlmutter, R.M., Taniguchi, T. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  37. B-cell growth factor: distinction from T-cell growth factor and B-cell maturation factor. Leanderson, T., Lundgren, E., Ruuth, E., Borg, H., Persson, H., Coutinho, A. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  38. Receptor antagonist and selective agonist derivatives of mouse interleukin-2. Zurawski, S.M., Zurawski, G. EMBO J. (1992) [Pubmed]
  39. Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene. Lécine, P., Algarté, M., Rameil, P., Beadling, C., Bucher, P., Nabholz, M., Imbert, J. Mol. Cell. Biol. (1996) [Pubmed]
  40. Interleukin 1 augments the expression of the interleukin 2 receptor alpha-chain in interleukin 6-stimulated myeloid cells by a transcriptional and posttranscriptional mechanism. Ruhl, S., Schwabe, M., Pluznik, D.H. Exp. Hematol. (1992) [Pubmed]
  41. Interleukin 2-mediated uncoupling of T cell receptor alpha/beta from CD3 signaling. Haughn, L., Leung, B., Boise, L., Veillette, A., Thompson, C., Julius, M. J. Exp. Med. (1998) [Pubmed]
  42. The amino terminus of JAK3 is necessary and sufficient for binding to the common gamma chain and confers the ability to transmit interleukin 2-mediated signals. Chen, M., Cheng, A., Chen, Y.Q., Hymel, A., Hanson, E.P., Kimmel, L., Minami, Y., Taniguchi, T., Changelian, P.S., O'Shea, J.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  43. The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation. Ravichandran, K.S., Burakoff, S.J. J. Biol. Chem. (1994) [Pubmed]
  44. The absence of Tssc6, a member of the tetraspanin superfamily, does not affect lymphoid development but enhances in vitro T-cell proliferative responses. Tarrant, J.M., Groom, J., Metcalf, D., Li, R., Borobokas, B., Wright, M.D., Tarlinton, D., Robb, L. Mol. Cell. Biol. (2002) [Pubmed]
  45. Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. McCaffrey, P.G., Luo, C., Kerppola, T.K., Jain, J., Badalian, T.M., Ho, A.M., Burgeon, E., Lane, W.S., Lambert, J.N., Curran, T. Science (1993) [Pubmed]
  46. Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice. Rapoport, M.J., Jaramillo, A., Zipris, D., Lazarus, A.H., Serreze, D.V., Leiter, E.H., Cyopick, P., Danska, J.S., Delovitch, T.L. J. Exp. Med. (1993) [Pubmed]
  47. Differential regulation of interleukin 4 and interleukin 5 gene expression: a comparison of T-cell gene induction by anti-CD3 antibody or by exogenous lymphokines. Bohjanen, P.R., Okajima, M., Hodes, R.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  48. Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia. Okamoto, M., Kato, S., Oizumi, K., Kinoshita, M., Inoue, Y., Hoshino, K., Akira, S., McKenzie, A.N., Young, H.A., Hoshino, T. Blood (2002) [Pubmed]
  49. Stem cell factor enhances interleukin-2-mediated expansion of murine natural killer cells in vivo. Fehniger, T.A., Carson, W.E., Mrózek, E., Caligiuri, M.A. Blood (1997) [Pubmed]
  50. A novel role of IL-2 in organ-specific autoimmune inflammation beyond regulatory T cell checkpoint: both IL-2 knockout and Fas mutation prolong lifespan of Scurfy mice but by different mechanisms. Zheng, L., Sharma, R., Gaskin, F., Fu, S.M., Ju, S.T. J. Immunol. (2007) [Pubmed]
  51. Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor. Widmer, M.B., Grabstein, K.H. Nature (1987) [Pubmed]
  52. IL-15 and IL-2: a matter of life and death for T cells in vivo. Li, X.C., Demirci, G., Ferrari-Lacraz, S., Groves, C., Coyle, A., Malek, T.R., Strom, T.B. Nat. Med. (2001) [Pubmed]
  53. Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. Thomis, D.C., Gurniak, C.B., Tivol, E., Sharpe, A.H., Berg, L.J. Science (1995) [Pubmed]
  54. Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Hodge, M.R., Ranger, A.M., Charles de la Brousse, F., Hoey, T., Grusby, M.J., Glimcher, L.H. Immunity (1996) [Pubmed]
  55. An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction. Nakajima, H., Liu, X.W., Wynshaw-Boris, A., Rosenthal, L.A., Imada, K., Finbloom, D.S., Hennighausen, L., Leonard, W.J. Immunity (1997) [Pubmed]
  56. Cytokine gene transcription in vascularised organ grafts: analysis using semiquantitative polymerase chain reaction. Dallman, M.J., Larsen, C.P., Morris, P.J. J. Exp. Med. (1991) [Pubmed]
  57. Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the immunologically privileged central nervous system. Sampson, J.H., Archer, G.E., Ashley, D.M., Fuchs, H.E., Hale, L.P., Dranoff, G., Bigner, D.D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
WikiGenes - Universities