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Interleukin 2

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Encyclopedia of Signaling Molecules

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References

  • Ballesteros-Tato A, Leon B, Graf BA, Moquin A, Adams PS, Lund FE, et al. Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation. Immunity. 2012;36:847–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bright R, Coventry BJ, Eardley-Harris N, Briggs N. Clinical response rates from interleukin-2 therapy for metastatic melanoma over 30 years’ experience: a meta-analysis of 3312 patients. J Immunother. 2017;40:21–30.

    Article  PubMed  CAS  Google Scholar 

  • Burchill MA, Yang J, Vang KB, Moon JJ, Chu HH, Lio CW, et al. Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity. 2008;28:112–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheng G, Yuan X, Tsai MS, Podack ER, Yu A, Malek TR. IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells. J Immunol. 2012;189:1780–91.

    Article  PubMed  CAS  Google Scholar 

  • Cheng G, Yu A, Dee MJ, Malek TR. IL-2R signaling is essential for functional maturation of regulatory T cells during thymic development. J Immunol. 2013;190:1567–75.

    Article  PubMed  CAS  Google Scholar 

  • Churlaud G, Jimenez V, Ruberte J, Amadoudji Zin M, Fourcade G, Gottrand G, Casana E, Lambrecht B, Bellier B, Piaggio E, et al. Sustained stimulation and expansion of Tregs by IL-2 control autoimmunity without impairing immune responses to infection, vaccination and cancer. Clin Immunol. 2014;151:114–26.

    Article  PubMed  CAS  Google Scholar 

  • Cote-Sierra J, Foucras G, Guo L, Chiodetti L, Young HA, Hu-Li J, et al. Interleukin 2 plays a central role in Th2 differentiation. Proc Natl Acad Sci USA. 2004;101:3880–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Davidson TS, DiPaolo RJ, Andersson J, Shevach EM. Cutting edge: IL-2 is essential for TGF-β-mediated induction of Foxp3+ T regulatory cells. J Immunol. 2007;178:4022–6.

    Article  PubMed  CAS  Google Scholar 

  • Dooms H, Wolslegel K, Lin P, Abbas AK. Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7R alpha-expressing cells. J Exp Med. 2007;204:547–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity. 2005;22:329–41.

    Article  PubMed  CAS  Google Scholar 

  • Hartemann A, Bensimon G, Payan CA, Jacqueminet S, Bourron O, Nicolas N, Fonfrede M, Rosenzwajg M, Bernard C, Klatzmann D. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013;1:295–305.

    Article  PubMed  CAS  Google Scholar 

  • Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, et al. Inflammation directs memory precursor and short-lived effector CD8+ T cell fates via the graded expression of T-bet transcription factor. Immunity. 2007;27:281–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kalia V, Sarkar S, Subramaniam S, Haining WN, Smith KA, Ahmed R. Prolonged interleukin-2Rα expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity. 2010;32:91–103.

    Article  PubMed  CAS  Google Scholar 

  • Kitas GD, Salmon M, Farr M, Gaston JS, Bacon PA. Deficient interleukin 2 production in rheumatoid arthritis: association with active disease and systemic complications. Clin Exp Immunol. 1988;73:242–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol. 2015;15:283–94.

    Article  CAS  PubMed  Google Scholar 

  • Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea III EP, Armand P, Cutler C, Ho VT, Treister NS, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365:2055–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity. 2007;26:371–81.

    Article  CAS  PubMed  Google Scholar 

  • Li YR, Li J, Zhao SD, Bradfield JP, Mentch FD, Maggadottir SM, Hou C, Abrams DJ, Chang D, Gao F, et al. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases. Nat Med. 2015;21:1018–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liao W, Lin JX, Wang L, Li P, Leonard WJ. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages. Nat Immunol. 2011;12:551–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lieberman LA, Tsokos GC. The IL-2 defect in systemic lupus erythematosus disease has an expansive effect on host immunity. J Biomed Biotechnol. 2010;740619.

    Google Scholar 

  • Lio CW, Hsieh CS. A two-step process for thymic regulatory T cell development. Immunity. 2008;28:100–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell. 2010;140:845–58.

    Article  CAS  PubMed  Google Scholar 

  • Malek TR. The biology of interleukin-2. Annu Rev Immunol. 2008;26:453–79.

    Article  CAS  PubMed  Google Scholar 

  • Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity. 2010;33:153–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Malek TR, Yu A, Vincek V, Scibelli P, Kong L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rβ-deficient mice. Implications for the nonredundant function of IL-2. Immunity. 2002;17:167–78.

    Article  CAS  PubMed  Google Scholar 

  • Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011;186:3299–303.

    Article  PubMed  CAS  Google Scholar 

  • Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976;193:1007–8.

    Article  CAS  PubMed  Google Scholar 

  • Nelson BH, Willerford DM. Biology of the interleukin-2 receptor. Adv Immunol. 1998;70:1–81.

    Article  CAS  PubMed  Google Scholar 

  • Pipkin ME, Sacks JA, Cruz-Guilloty F, Lichtenheld MG, Bevan MJ, Rao A. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity. 2010;32:79–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Raynor J, Sholl A, Plas DR, Bouillet P, Chougnet CA, Hildeman DA. IL-15 fosters age-driven regulatory T cell accrual in the face of declining IL-2 levels. T Cell Biol. 2013;4:161.

    CAS  Google Scholar 

  • Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 2014;192:5451–8.

    Article  CAS  PubMed  Google Scholar 

  • Rosenzwajg M, Churlaud G, Mallone R, Six A, Dérian N, Chaara W, Lorenzon R, Long SA, Buckner JH, Afonso G, et al. Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients. J Autoimmun. 2015;58:48–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011;365:2067–77.

    Article  CAS  PubMed  Google Scholar 

  • Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell. 1993;75:253–61.

    Article  CAS  PubMed  Google Scholar 

  • Schorle H, Holtschke T, Hunig T, Shimpl A, Horak I. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature. 1991;352:621–4.

    Article  CAS  PubMed  Google Scholar 

  • Smigiel KS, Richards E, Srivastava S, Thomas KR, Dudda JC, Klonowski KD, et al. CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets. J Exp Med. 2014;211:121–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Smith KA. Interleukin-2: inception, impact, and implications. Science. 1988;240:1169–76.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki H, Kundig TM, Furlonger C, Wakeham A, Timms E, Matsuyama T, Schmits R, Simard JJ, Ohashi PS, Griesser H, et al. Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta. Science. 1995;268:1472–6.

    Article  CAS  PubMed  Google Scholar 

  • Willerford DM, Chen J, Ferry JA, Davidson L, Ma A, Alt FW. Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment. Immunity. 1995;3:521–30.

    Article  CAS  PubMed  Google Scholar 

  • Williams MA, Tyznik AJ, Bevan MJ. Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature. 2006;441:890–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yu A, Zhu L, Altman NH, Malek TR. A low interleukin-2 receptor signaling threshold supports the development and homeostasis of T regulatory cells. Immunity. 2009;30:204–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature. 2010;463:808–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zier KS, Leo MM, Spielman RS, Baker L. Decreased synthesis of interleukin-2 (IL-2) in insulin-dependent diabetes mellitus. Diabetes. 1984;33:552–5.

    Article  CAS  PubMed  Google Scholar 

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Klatzmann, D., Malek, T.R. (2018). Interleukin 2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101968

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