Il2

Summary

Gene Symbol: Il2
Description: interleukin 2
Alias: Il-2, interleukin-2, T-cell growth factor, TCGF
Species: mouse
Products:     Il2

Top Publications

  1. Behrens G, Li M, Davey G, Allison J, Flavell R, Carbone F, et al. Helper requirements for generation of effector CTL to islet beta cell antigens. J Immunol. 2004;172:5420-6 pubmed
    ..This provides insight into the helper requirements for adoptive transfer immunotherapy of tumors and suggests key points for inhibition of CTL-mediated autoimmunity. ..
  2. Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner V, et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet. 2007;39:329-37 pubmed
    ..in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory ..
  3. D Souza W, Lefrancois L. IL-2 is not required for the initiation of CD8 T cell cycling but sustains expansion. J Immunol. 2003;171:5727-35 pubmed
    ..Thus, activated CD8 T cells initially undergo IL-2-independent proliferation, but reach a critical juncture where the requirement for IL-2 as a growth factor gains prominence. ..
  4. Rakoff Nahoum S, Hao L, Medzhitov R. Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity. 2006;25:319-29 pubmed
    ..We report that colitis was dependent on TLR signaling in Il10(-/-) mice. In contrast, Il2(-/-) mice developed intestinal inflammation in the absence of TLR signaling pathways...
  5. Li X, Demirci G, Ferrari Lacraz S, Groves C, Coyle A, Malek T, et al. IL-15 and IL-2: a matter of life and death for T cells in vivo. Nat Med. 2001;7:114-8 pubmed
    ..Our study provides data that IL-2 and IL-15 regulate distinct aspects of primary T-cell expansion in vivo. ..
  6. D Cruz L, Klein L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol. 2005;6:1152-9 pubmed
    b>Interleukin 2 signaling is believed to be critically involved in several aspects of CD25(+) CD4(+) regulatory T cell biology, such as intrathymic development, peripheral survival and suppressive function...
  7. Malek T, Yu A, Vincek V, Scibelli P, Kong L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity. 2002;17:167-78 pubmed
    ..These observations indicate that the essential function of the IL-2/IL-2R system primarily lies at the level of the production of CD4(+)CD25(+) regulatory T cells. ..
  8. Almeida A, Legrand N, Papiernik M, Freitas A. Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers. J Immunol. 2002;169:4850-60 pubmed
  9. Villarino A, Tato C, Stumhofer J, Yao Z, Cui Y, Hennighausen L, et al. Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals. J Exp Med. 2007;204:65-71 pubmed
  10. Knoechel B, Lohr J, Kahn E, Bluestone J, Abbas A. Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J Exp Med. 2005;202:1375-86 pubmed
    ..Thus, a peripheral T cell reaction to a systemic antigen goes through a phase of effector cell-mediated pathology followed by T reg cell-mediated recovery, and both require the growth factor IL-2. ..

Detail Information

Publications69

  1. Behrens G, Li M, Davey G, Allison J, Flavell R, Carbone F, et al. Helper requirements for generation of effector CTL to islet beta cell antigens. J Immunol. 2004;172:5420-6 pubmed
    ..This provides insight into the helper requirements for adoptive transfer immunotherapy of tumors and suggests key points for inhibition of CTL-mediated autoimmunity. ..
  2. Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner V, et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet. 2007;39:329-37 pubmed
    ..in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory ..
  3. D Souza W, Lefrancois L. IL-2 is not required for the initiation of CD8 T cell cycling but sustains expansion. J Immunol. 2003;171:5727-35 pubmed
    ..Thus, activated CD8 T cells initially undergo IL-2-independent proliferation, but reach a critical juncture where the requirement for IL-2 as a growth factor gains prominence. ..
  4. Rakoff Nahoum S, Hao L, Medzhitov R. Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity. 2006;25:319-29 pubmed
    ..We report that colitis was dependent on TLR signaling in Il10(-/-) mice. In contrast, Il2(-/-) mice developed intestinal inflammation in the absence of TLR signaling pathways...
  5. Li X, Demirci G, Ferrari Lacraz S, Groves C, Coyle A, Malek T, et al. IL-15 and IL-2: a matter of life and death for T cells in vivo. Nat Med. 2001;7:114-8 pubmed
    ..Our study provides data that IL-2 and IL-15 regulate distinct aspects of primary T-cell expansion in vivo. ..
  6. D Cruz L, Klein L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol. 2005;6:1152-9 pubmed
    b>Interleukin 2 signaling is believed to be critically involved in several aspects of CD25(+) CD4(+) regulatory T cell biology, such as intrathymic development, peripheral survival and suppressive function...
  7. Malek T, Yu A, Vincek V, Scibelli P, Kong L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity. 2002;17:167-78 pubmed
    ..These observations indicate that the essential function of the IL-2/IL-2R system primarily lies at the level of the production of CD4(+)CD25(+) regulatory T cells. ..
  8. Almeida A, Legrand N, Papiernik M, Freitas A. Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers. J Immunol. 2002;169:4850-60 pubmed
  9. Villarino A, Tato C, Stumhofer J, Yao Z, Cui Y, Hennighausen L, et al. Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals. J Exp Med. 2007;204:65-71 pubmed
  10. Knoechel B, Lohr J, Kahn E, Bluestone J, Abbas A. Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J Exp Med. 2005;202:1375-86 pubmed
    ..Thus, a peripheral T cell reaction to a systemic antigen goes through a phase of effector cell-mediated pathology followed by T reg cell-mediated recovery, and both require the growth factor IL-2. ..
  11. Jones T, Ha J, Williams M, Adams A, Durham M, Rees P, et al. The role of the IL-2 pathway in costimulation blockade-resistant rejection of allografts. J Immunol. 2002;168:1123-30 pubmed
    ..Interestingly, depletion of CD4+ T cells, but not CD8+ cells, prevents prolongation in allograft survival, suggesting an IL-2-independent role for regulation in extended survival. ..
  12. Wiesel M, Joller N, Ehlert A, Crouse J, Spörri R, Bachmann M, et al. Th cells act via two synergistic pathways to promote antiviral CD8+ T cell responses. J Immunol. 2010;185:5188-97 pubmed publisher
    ..Second, Th cells provide CD8(+) T cells with IL-2, thereby enhancing their survival. Thus, Th cells are at the center of an important communication loop with a central role for IL-2/IL-2R and bioactive IL-12. ..
  13. Miller J, Stevens E, Smith D, Wight T, Wrenshall L. Perlecan: a major IL-2-binding proteoglycan in murine spleen. Immunol Cell Biol. 2008;86:192-9 pubmed
    ..Identification of perlecan as a major heparan sulfate proteoglycan that binds IL-2 has implications for both the localization and regulation of IL-2 in vivo. ..
  14. Wang G, Khattar M, Guo Z, Miyahara Y, Linkes S, Sun Z, et al. IL-2-deprivation and TGF-beta are two non-redundant suppressor mechanisms of CD4+CD25+ regulatory T cell which jointly restrain CD4+CD25- cell activation. Immunol Lett. 2010;132:61-8 pubmed publisher
    ..In conclusion, these two suppressive mechanisms acting in concert may be necessary to effectively restrain the early activation of Tconvs. ..
  15. Nagahama K, Ogawa A, Shirane K, Shimomura Y, Sugimoto K, Mizoguchi A. Protein kinase C theta plays a fundamental role in different types of chronic colitis. Gastroenterology. 2008;134:459-69 pubmed
    ..PKCtheta serves as a common and fundamental signaling molecule in the development of different types of colitis and may represent an attractive target for treating inflammatory bowel disease. ..
  16. Barron L, Dooms H, Hoyer K, Kuswanto W, Hofmann J, O Gorman W, et al. Cutting edge: mechanisms of IL-2-dependent maintenance of functional regulatory T cells. J Immunol. 2010;185:6426-30 pubmed publisher
  17. Cho J, Boyman O, Kim H, Hahm B, Rubinstein M, Ramsey C, et al. An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2. J Exp Med. 2007;204:1787-801 pubmed
    ..IL-2/IL-15) concerned. The relevance of the data to the gradual transition of naive T cells into memory-phenotype (MP) cells with age is discussed. ..
  18. Bayer A, Yu A, Adeegbe D, Malek T. Essential role for interleukin-2 for CD4(+)CD25(+) T regulatory cell development during the neonatal period. J Exp Med. 2005;201:769-77 pubmed
    ..However, for normal neonates, blockade of IL-2 decreased T(reg) cells in both the thymus and LN. Therefore, two steps of T(reg) cell development depend upon IL-2 in neonatal mice, thymus production, and subsequent expansion in the LN. ..
  19. de la Rosa M, Rutz S, Dorninger H, Scheffold A. Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur J Immunol. 2004;34:2480-8 pubmed
    ..We propose the parakrine uptake of soluble mediators as a flexible mechanism to adapt Treg activity to the strength of the responder T cell reaction. ..
  20. Vosshenrich C, Ranson T, Samson S, Corcuff E, Colucci F, Rosmaraki E, et al. Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J Immunol. 2005;174:1213-21 pubmed
    ..Surprisingly, the few residual NK cells generated in absence of IL-15 appear relatively mature, expressing a variety of Ly49 receptors and demonstrating lytic and cytokine production capacity. ..
  21. McNally A, Hill G, Sparwasser T, Thomas R, Steptoe R. CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proc Natl Acad Sci U S A. 2011;108:7529-34 pubmed publisher
    ..Furthermore, a regulatory loop exists between Treg and CD8(+) effector T cells, where IL-2 produced during CD8(+) T-cell effector differentiation promotes Treg expansion. ..
  22. Williams M, Tyznik A, Bevan M. Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature. 2006;441:890-3 pubmed
    ..These results have important implications for the development of vaccination or immunotherapeutic strategies aimed at boosting memory T-cell function. ..
  23. Wrenshall L, Platt J, Stevens E, Wight T, Miller J. Propagation and control of T cell responses by heparan sulfate-bound IL-2. J Immunol. 2003;170:5470-4 pubmed
    ..These findings necessitate a new look at how IL-2 regulates immune responses and support the notion that the microenvironment plays a determining role in modulating the character of immune responses. ..
  24. Nelson B. Interleukin-2 signaling and the maintenance of self-tolerance. Curr Dir Autoimmun. 2002;5:92-112 pubmed
    ..In this regard, perhaps new insights into this important issue can be gained by better defining when and where IL-2 signaling normally occurs in wild-type animals and the functional status of the T cells involved. ..
  25. Antov A, Yang L, Vig M, Baltimore D, Van Parijs L. Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance. J Immunol. 2003;171:3435-41 pubmed
    ..Furthermore, transient activation of STAT5 is sufficient to increase CD25(+)CD4(+) T reg numbers in IL-2-deficient mice. Our study uncovers an essential role for STAT5 in maintaining CD25(+)CD4(+) T reg homeostasis and self-tolerance. ..
  26. Chen Y, Haines C, Gutcher I, Hochweller K, Blumenschein W, McClanahan T, et al. Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2. Immunity. 2011;34:409-21 pubmed publisher
    ..Rather, regulation of IL-2 availability and resultant signaling through CD25 by Treg cells was found to play an important role. ..
  27. Dooms H, Wolslegel K, Lin P, Abbas A. Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7R alpha-expressing cells. J Exp Med. 2007;204:547-57 pubmed
    ..These results identify IL-2 as a factor regulating IL-7Ralpha expression and, consequently, memory T cell homeostasis in vivo. ..
  28. Krutzik P, Clutter M, Nolan G. Coordinate analysis of murine immune cell surface markers and intracellular phosphoproteins by flow cytometry. J Immunol. 2005;175:2357-65 pubmed
  29. Guo Z, Khattar M, Schroder P, Miyahara Y, Wang G, He X, et al. A dynamic dual role of IL-2 signaling in the two-step differentiation process of adaptive regulatory T cells. J Immunol. 2013;190:3153-62 pubmed publisher
    ..These findings advance the understanding of iTreg differentiation and may facilitate the therapeutic use of iTregs in immune disorders. ..
  30. Dai Z, Konieczny B, Lakkis F. The dual role of IL-2 in the generation and maintenance of CD8+ memory T cells. J Immunol. 2000;165:3031-6 pubmed
    ..Thus, IL-2-based vaccine strategies or immunosuppressive regimens that target IL-2 should take into account the divergent roles of IL-2 in CD8+ T cell immunity. ..
  31. Fontenot J, Rasmussen J, Gavin M, Rudensky A. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol. 2005;6:1142-51 pubmed
    ..Most T(reg) cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in T(reg) cell biology has remained ..
  32. Bihl F, Pecheur J, Breart B, Poupon G, Cazareth J, Julia V, et al. Primed antigen-specific CD4+ T cells are required for NK cell activation in vivo upon Leishmania major infection. J Immunol. 2010;185:2174-81 pubmed publisher
    ..Our results reveal an unappreciated role for Ag-specific CD4(+) T cells in the initiation of NK cell activation in vivo upon L. major infection and demonstrate bidirectional regulations between innate and adaptive immunity. ..
  33. Liao W, Lin J, Wang L, Li P, Leonard W. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages. Nat Immunol. 2011;12:551-9 pubmed publisher
    ..T(H)1 differentiation was also impaired in mouse Il2(-/-) T cells but was restored by IL-12R?2 expression...
  34. Yang X, Ghoreschi K, Steward Tharp S, Rodriguez Canales J, Zhu J, Grainger J, et al. Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol. 2011;12:247-54 pubmed publisher
    b>Interleukin 2 (IL-2), a cytokine linked to human autoimmune disease, limits IL-17 production...
  35. Nelson B. IL-2, regulatory T cells, and tolerance. J Immunol. 2004;172:3983-8 pubmed
    IL-2 is a potent T cell growth factor that for many years was assumed to amplify lymphocyte responses in vivo...
  36. Qui H, Hagymasi A, Bandyopadhyay S, St Rose M, Ramanarasimhaiah R, Menoret A, et al. CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J Immunol. 2011;187:3555-64 pubmed publisher
    ..This mechanism might be therapeutically useful because CD134 plus CD137 dual costimulation induced CD4 T cell-dependent tumoricidal function in a mouse melanoma model. ..
  37. Wolf M, Schimpl A, Hunig T. Control of T cell hyperactivation in IL-2-deficient mice by CD4(+)CD25(-) and CD4(+)CD25(+) T cells: evidence for two distinct regulatory mechanisms. Eur J Immunol. 2001;31:1637-45 pubmed
    ..IL-2 deficiency therefore may upset T cell homeostasis by two distinct mechanisms: the failure to program expanding T cells for apoptosis, and the failure to generate functional CD4(+)CD25(+) regulatory cells. ..
  38. Burchill M, Yang J, Vogtenhuber C, Blazar B, Farrar M. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol. 2007;178:280-90 pubmed
    ..Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2Rbeta-dependent STAT5 activation promotes Treg differentiation by regulating expression of foxp3. ..
  39. Almeida A, Zaragoza B, Freitas A. Indexation as a novel mechanism of lymphocyte homeostasis: the number of CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cells. J Immunol. 2006;177:192-200 pubmed
    ..The present study highlights that maintenance of proportions between different lymphocyte subsets may also be critical for the immune system and are under strict homeostatic control. ..
  40. Laurence A, Tato C, Davidson T, Kanno Y, Chen Z, Yao Z, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity. 2007;26:371-81 pubmed
    ..We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2. ..
  41. Ghiasi H, Osorio Y, Perng G, Nesburn A, Wechsler S. Overexpression of interleukin-2 by a recombinant herpes simplex virus type 1 attenuates pathogenicity and enhances antiviral immunity. J Virol. 2002;76:9069-78 pubmed
    ..These results suggest that IL-2 expression by recombinant HSV-1 reduces virulence and that depletion of IL-2 or T cells increases virulence in HSV-1-infected mice. ..
  42. Bae J, Park D, Lee Y, Jeoung D. Interleukin-2 promotes angiogenesis by activation of Akt and increase of ROS. J Microbiol Biotechnol. 2008;18:377-82 pubmed
    ..IL-2 increased angiogenesis in an animal model and tube formation in HUVECs. The effect of IL-2 on angiogenesis and tube formation was mediated by ROS and Akt. This is the first report that IL-2 promotes angiogenesis. ..
  43. Mostbock S, Lutsiak M, Milenic D, Baidoo K, Schlom J, Sabzevari H. IL-2/anti-IL-2 antibody complex enhances vaccine-mediated antigen-specific CD8+ T cell responses and increases the ratio of effector/memory CD8+ T cells to regulatory T cells. J Immunol. 2008;180:5118-29 pubmed
    ..This phenomenon can thus potentially be used in the enhancement of immune responses to vaccination. ..
  44. Stahl M, Dijkers P, Kops G, Lens S, Coffer P, Burgering B, et al. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol. 2002;168:5024-31 pubmed
    ..Thus, we propose that inactivation of FoxO transcription factors by IL-2 plays a critical role in T cell proliferation and survival. ..
  45. Busse D, de la Rosa M, Hobiger K, Thurley K, Flossdorf M, Scheffold A, et al. Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. Proc Natl Acad Sci U S A. 2010;107:3058-63 pubmed publisher
    ..The present findings explain how IL-2 can play two distinct roles in immune regulation and point to a hitherto largely unexplored spatiotemporal complexity of cytokine signaling. ..
  46. Yamashita M, Ukai Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A, et al. Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci. J Biol Chem. 2004;279:26983-90 pubmed
    ..Thus, GATA3 plays important roles in the maintenance of the Th2 phenotype and continuous chromatin remodeling of the specific Th2 cytokine gene locus through cell division. ..
  47. Humrich J, Morbach H, Undeutsch R, Enghard P, Rosenberger S, Weigert O, et al. Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci U S A. 2010;107:204-9 pubmed publisher
    ..The reversibility of this homeostatic Treg disorder provides promising approaches for the treatment of SLE. ..
  48. Adachi S, Rothenberg E. Cell-type-specific epigenetic marking of the IL2 gene at a distal cis-regulatory region in competent, nontranscribing T-cells. Nucleic Acids Res. 2005;33:3200-10 pubmed
    ..heritably for activation, we have used chromatin immunoprecipitation to map histone modifications across the murine IL2 locus, from -10.2 through +0.25 kb, in induction-competent and incompetent cells...
  49. Liu Y, Zhang P, Li J, Kulkarni A, Perruche S, Chen W. A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Nat Immunol. 2008;9:632-40 pubmed publisher
    ..recovery of Foxp3+ thymocytes was attributable mainly to overproduction of and heightened responsiveness to interleukin 2, as genetic ablation of interleukin 2 in TbetaRI-mutant mice resulted in a complete absence of CD4+CD25+Foxp3+ ..
  50. Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005;201:723-35 pubmed
    ..Furthermore, impairment of this negative feedback loop via IL-2 can be a cause and a predisposing factor for autoimmune disease. ..
  51. Gong D, Malek T. Cytokine-dependent Blimp-1 expression in activated T cells inhibits IL-2 production. J Immunol. 2007;178:242-52 pubmed
    ..Collectively, these findings indicate that there is a negative feedback regulatory loop in activated T cells such that IL-2 inhibits its own production through induction of Blimp-1 while promoting an effector cell phenotype. ..
  52. Liao W, Schones D, Oh J, Cui Y, Cui K, Roh T, et al. Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression. Nat Immunol. 2008;9:1288-96 pubmed publisher
    ..expression, T cell receptor-induced IL-4Ralpha expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells. Notably, forced IL-4Ralpha expression restored the T(H)2 differentiation of Il2(-/-) cells...
  53. Wilson E, Livingstone A. Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses. J Immunol. 2008;181:7445-8 pubmed
    ..We suggest that it is also a critical component of help for CD8(+) T cell responses to pathogens, because protective memory also requires CD8(+) T cell stimulation by IL-2 during priming. ..
  54. Chen Q, Kim Y, Laurence A, Punkosdy G, Shevach E. IL-2 controls the stability of Foxp3 expression in TGF-beta-induced Foxp3+ T cells in vivo. J Immunol. 2011;186:6329-37 pubmed publisher
    ..Administration of IL-2 in vivo results in stabilization of Foxp3 expression and may prove to be a valuable adjunct for the use of iTreg for the treatment of autoimmune diseases. ..
  55. Gasteiger G, Hemmers S, Firth M, Le Floc h A, Huse M, Sun J, et al. IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells. J Exp Med. 2013;210:1167-78 pubmed publisher
    ..Our results suggest that IL-2-dependent adaptive-innate lymphocyte cross talk tunes NK cell reactivity and that T reg cells restrain NK cell cytotoxicity by limiting the availability of IL-2. ..
  56. Waithman J, Gebhardt T, Davey G, Heath W, Carbone F. Cutting edge: Enhanced IL-2 signaling can convert self-specific T cell response from tolerance to autoimmunity. J Immunol. 2008;180:5789-93 pubmed
    ..Therefore, enhanced IL-2 signaling can act as a major selector between tolerance and autoimmunity. ..
  57. Pipkin M, Sacks J, Cruz Guilloty F, Lichtenheld M, Bevan M, Rao A. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity. 2010;32:79-90 pubmed publisher
    ..Thus, inflammation influences both effector and memory CTL differentiation, whereas persistent IL-2 stimulation promotes effector at the expense of memory CTL development...
  58. Janas M, Groves P, Kienzle N, Kelso A. IL-2 regulates perforin and granzyme gene expression in CD8+ T cells independently of its effects on survival and proliferation. J Immunol. 2005;175:8003-10 pubmed
    ..Together, these findings indicate that IL-2 can directly regulate perforin and granzyme gene expression in CD8+ T cells independently of its effects on cell survival and proliferation. ..
  59. Dooms H, Kahn E, Knoechel B, Abbas A. IL-2 induces a competitive survival advantage in T lymphocytes. J Immunol. 2004;172:5973-9 pubmed
    ..Therefore, IL-2 enhances competitiveness for survival in CD4(+) T cells, thereby facilitating the development of a memory population. ..
  60. Martins G, Cimmino L, Liao J, Magnusdottir E, Calame K. Blimp-1 directly represses Il2 and the Il2 activator Fos, attenuating T cell proliferation and survival. J Exp Med. 2008;205:1959-65 pubmed publisher
    ..that one critical activity of Blimp-1 in T cells is to repress IL-2, and that it does so by direct repression of Il2 transcription, and also by repression of Fos transcription...
  61. Waidmann M, Bechtold O, Frick J, Lehr H, Schubert S, Dobrindt U, et al. Bacteroides vulgatus protects against Escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice. Gastroenterology. 2003;125:162-77 pubmed
    ..In IL-2-/- mice, B. vulgatus mpk protects against E. coli mpk-triggered colitis by an unknown mechanism. E. coli Nissle does not induce colitis. Various bacterial species common to the microflora differ in their ability to trigger IBD. ..
  62. Kang H, Zhang D, Degauque N, Mariat C, Alexopoulos S, Zheng X. Effects of cyclosporine on transplant tolerance: the role of IL-2. Am J Transplant. 2007;7:1907-16 pubmed
    ..The combination of IL-2/Fc and cyclosporine treatment may provide a new clinical strategy to promote transplant tolerance. ..
  63. Sitrin J, Ring A, Garcia K, Benoist C, Mathis D. Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2. J Exp Med. 2013;210:1153-65 pubmed publisher
    ..Our findings highlight the need to consider potential effects on NK cells when designing therapeutic strategies based on manipulation of IL-2 levels or targets. ..
  64. Létourneau S, van Leeuwen E, Krieg C, Martin C, Pantaleo G, Sprent J, et al. IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. Proc Natl Acad Sci U S A. 2010;107:2171-6 pubmed publisher
    ..These data suggest an unpredicted role for CD25 in IL-2 homeostasis. ..
  65. Sharma R, Fu S, Ju S. IL-2: a two-faced master regulator of autoimmunity. J Autoimmun. 2011;36:91-7 pubmed publisher
    ..Whether IL-2 is also required for autoimmune disease development is less clear as Il2(-/)(-) mice themselves spontaneously develop multi-organ inflammation (MOI)...
  66. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo M. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8:1353-62 pubmed
    ..Thus, cytokine deprivation-induced apoptosis is a prominent mechanism by which T(reg) cells inhibit effector T cell responses. ..
  67. French A, Sjölin H, Kim S, Koka R, Yang L, Young D, et al. DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infections. J Immunol. 2006;177:4981-90 pubmed
    ..The impact of Ly49H-mediated signaling on NK cell proliferation is masked in the presence of high concentrations of proproliferative cytokines that nonselectively drive all NK cells to proliferate. ..
  68. Oestreich K, Mohn S, Weinmann A. Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile. Nat Immunol. 2012;13:405-11 pubmed publisher
    ..Here we found that high concentrations of interleukin 2 (IL-2) inhibited Bcl-6 expression in polarized T(H)1 cells...
  69. Vang K, Yang J, Mahmud S, Burchill M, Vegoe A, Farrar M. IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development. J Immunol. 2008;181:3285-90 pubmed