interleukin 15


Summary: Cytokine that stimulates the proliferation of T-LYMPHOCYTES and shares biological activities with IL-2. IL-15 also can induce proliferation and differentiation of B-LYMPHOCYTES.

Top Publications

  1. Berger C, Berger M, Hackman R, Gough M, Elliott C, Jensen M, et al. Safety and immunologic effects of IL-15 administration in nonhuman primates. Blood. 2009;114:2417-26 pubmed publisher
    ..These findings demonstrate that IL-15 has profound immunomodulatory properties distinct from those described for IL-2, and suggest that intermittent administration of IL-15 should be considered in clinical studies. ..
  2. Hardy M, Kassianos A, Vulink A, Wilkinson R, Jongbloed S, Hart D, et al. NK cells enhance the induction of CTL responses by IL-15 monocyte-derived dendritic cells. Immunol Cell Biol. 2009;87:606-14 pubmed publisher
    ..These data implicate a role for small percentages of NK cells in the enhanced capacity of IL-15 MoDC to induce tumour-specific CTL independent of IL-12p70. ..
  3. Chirifu M, Hayashi C, Nakamura T, Toma S, Shuto T, Kai H, et al. Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans. Nat Immunol. 2007;8:1001-7 pubmed
    b>Interleukin 15 (IL-15) and IL-2, which promote the survival of memory CD8(+) T cells and regulatory T cells, respectively, bind receptor complexes that share beta- and gamma-signaling subunits...
  4. Mathers A, Janelsins B, Rubin J, Tkacheva O, Shufesky W, Watkins S, et al. Differential capability of human cutaneous dendritic cell subsets to initiate Th17 responses. J Immunol. 2009;182:921-33 pubmed
    ..Overall, our data demonstrate that human epidermal smiLCs induce Th17 responses by mechanisms different from those previously described and highlight the need to target clinical treatments based on these variations. ..
  5. Quintarelli C, Vera J, Savoldo B, Giordano Attianese G, Pule M, Foster A, et al. Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes. Blood. 2007;110:2793-802 pubmed
    ..We found that the incorporation of an inducible caspase-9 suicide gene allowed efficient elimination of transgenic CTLs after exposure to a chemical inducer of dimerization, thereby increasing the safety and feasibility of the approach. ..
  6. Bouchaud G, Garrigue Antar L, Solé V, Quéméner A, Boublik Y, Mortier E, et al. The exon-3-encoded domain of IL-15ralpha contributes to IL-15 high-affinity binding and is crucial for the IL-15 antagonistic effect of soluble IL-15Ralpha. J Mol Biol. 2008;382:1-12 pubmed publisher
    ..The soluble IL-15Ralpha sushi domain-IL-15 fusion protein is therefore able to bind and activate both the IL-15Rbeta/gamma and the IL-15Ralpha/beta/gamma receptors. ..
  7. Zhou H, Huang H, Shi J, Zhao Y, Dong Q, Jia H, et al. Prognostic value of interleukin 2 and interleukin 15 in peritumoral hepatic tissues for patients with hepatitis B-related hepatocellular carcinoma after curative resection. Gut. 2010;59:1699-708 pubmed publisher
    ..95, p=0.025) was independent of other clinicopathological factors. Peritumoral IL-2 and IL-15 levels are useful for stratifying patients, even those with early-stage HCC, into subgroups with different prognoses after curative resection. ..
  8. Mueller Y, Do D, Altork S, Artlett C, Gracely E, Katsetos C, et al. IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T cell responses. J Immunol. 2008;180:350-60 pubmed
    ..Finally, IL-15-treated acutely SIV-infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection. ..
  9. Boyiadzis M, Memon S, Carson J, Allen K, Szczepanski M, Vance B, et al. Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels. Biol Blood Marrow Transplant. 2008;14:290-300 pubmed publisher

Scientific Experts

More Information


  1. Zheng X, Wang Y, Wei H, Ling B, Sun R, Tian Z. Bcl-xL is associated with the anti-apoptotic effect of IL-15 on the survival of CD56(dim) natural killer cells. Mol Immunol. 2008;45:2559-69 pubmed publisher
    ..So IL-15 played a crucial role in sustaining long-lasting functions of CD56(dim) NK cells. ..
  2. Joshi N, Cui W, Chandele A, Lee H, Urso D, 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 pubmed
    ..These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential. ..
  3. Hanick N, Rickert M, Varani L, Bankovich A, Cochran J, Kim D, et al. Elucidation of the interleukin-15 binding site on its alpha receptor by NMR. Biochemistry. 2007;46:9453-61 pubmed
    ..The interface, as predicted here, leaves open the possibility of trans-presentation of IL-15 by IL-15Ralpha on an opposing cell. ..
  4. Huntington N, Puthalakath H, Gunn P, Naik E, Michalak E, Smyth M, et al. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Nat Immunol. 2007;8:856-63 pubmed
    b>Interleukin 15 (IL-15) promotes the survival of natural killer (NK) cells by preventing apoptosis through mechanisms unknown at present. Here we identify Bim, Noxa and Mcl-1 as key regulators of IL-15-dependent survival of NK cells...
  5. Fehniger T, Cai S, Cao X, Bredemeyer A, Presti R, French A, et al. Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs. Immunity. 2007;26:798-811 pubmed
    ..These data suggest that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation. ..
  6. Johnson W, Bastos R, Davis W, Goff W. Bovine WC1(-) gammadeltaT cells incubated with IL-15 express the natural cytotoxicity receptor CD335 (NKp46) and produce IFN-gamma in response to exogenous IL-12 and IL-18. Dev Comp Immunol. 2008;32:1002-10 pubmed publisher
    ..Taken as a whole, we describe a new phenotypically distinct bovine gammadeltaT cell sub-population capable of participating in type 1 immune responses. ..
  7. Oh S, Perera L, Terabe M, Ni L, Waldmann T, Berzofsky J. IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis. Proc Natl Acad Sci U S A. 2008;105:5201-6 pubmed publisher
    ..These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency. ..
  8. Weger W, Hofer A, Wolf P, El Shabrawi Y, Renner W, Kerl H, et al. Role of the interleukin 15 96516A>T and IL15 96330C>A gene polymorphisms in Caucasian patients with chronic plaque psoriasis. J Dermatol Sci. 2008;51:147-9 pubmed publisher
  9. Duitman E, Orinska Z, Bulanova E, Paus R, Bulfone Paus S. How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor: lessons from interleukin-15 (IL-15)/IL-15 receptor alpha. Mol Cell Biol. 2008;28:4851-61 pubmed publisher
  10. Ben Ahmed M, Belhadj Hmida N, Moes N, Buyse S, Abdeladhim M, Louzir H, et al. IL-15 renders conventional lymphocytes resistant to suppressive functions of regulatory T cells through activation of the phosphatidylinositol 3-kinase pathway. J Immunol. 2009;182:6763-70 pubmed publisher
    ..This dual role may be instrumental to mount rapid but transient proinflammatory immune responses against pathogens but may become deleterious in situations associated with protracted IL-15 over-expression. ..
  11. Paxton R. Measurement of interleukin 15. Curr Protoc Immunol. 2001;Chapter 6:Unit 6.22 pubmed publisher
    b>Interleukin 15 (IL-15) is a small helical cytokine that was first characterized by its ability to stimulate proliferation of the murine T cell line CTLL-2, but is now known to have activity on a variety of cell types...
  12. Mortier E, Woo T, Advincula R, Gozalo S, Ma A. IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med. 2008;205:1213-25 pubmed publisher
    ..These studies define an unprecedented cytokine-receptor biosynthetic pathway in which IL-15Ralpha serves as a chaperone for IL-15, after which membrane-bound IL-15Ralpha-IL-15 complexes activate NK cells via direct cell-cell contact. ..
  13. Enose Akahata Y, Oh U, Grant C, Jacobson S. Retrovirally induced CTL degranulation mediated by IL-15 expression and infection of mononuclear phagocytes in patients with HTLV-I-associated neurologic disease. Blood. 2008;112:2400-10 pubmed publisher
    ..Despite lower viral expression than in CD4(+) T cells, HTLV-I-infected or -activated CD14(+) cells may be a heretofore important but under recognized reservoir particularly in HAM/TSP patients...
  14. Huntington N, Legrand N, Alves N, Jaron B, Weijer K, Plet A, et al. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med. 2009;206:25-34 pubmed publisher
  15. Kim H, Hwang K, Park S, Kang I. IL-7 and IL-15: biology and roles in T-Cell immunity in health and disease. Crit Rev Immunol. 2008;28:325-39 pubmed
    ..Here, we review what is currently known about the roles of these cytokines in T-cell immunity, in general, as well as in RA, in particular, focusing on recent discoveries. ..
  16. Sun J, Ma A, Lanier L. Cutting edge: IL-15-independent NK cell response to mouse cytomegalovirus infection. J Immunol. 2009;183:2911-4 pubmed publisher
    ..Together, these findings demonstrate a previously unrecognized independence of NK cells on IL-15 or other common gamma signaling cytokines during their response against viral infection. ..
  17. Walter J, Ghosh M, Kuhn L, Semrau K, Sinkala M, Kankasa C, et al. High concentrations of interleukin 15 in breast milk are associated with protection against postnatal HIV transmission. J Infect Dis. 2009;200:1498-502 pubmed publisher
    Given the central role that interleukin 15 (IL-15) plays in human immunodeficiency virus (HIV) immunity, we hypothesized that IL-15 in breast milk may protect against postnatal HIV transmission...
  18. Wu S, Fischer L, Gökbuget N, Schwartz S, Burmeister T, Notter M, et al. Expression of interleukin 15 in primary adult acute lymphoblastic leukemia. Cancer. 2010;116:387-92 pubmed publisher
    ..It remains to be evaluated whether IL-15 might be a relevant therapy target, or might be used for risk stratification. ..
  19. Gomez Nicola D, Valle Argos B, Pita Thomas D, Nieto Sampedro M. Interleukin 15 expression in the CNS: blockade of its activity prevents glial activation after an inflammatory injury. Glia. 2008;56:494-505 pubmed publisher
    ..Because IL-15 appears to modulate the inflammatory environment acutely generated after CNS injury, regulating IL-15 expression seems a clear antiinflammatory therapy to improve the outcome of neurodegenerative diseases and CNS trauma. ..
  20. Kagimoto Y, Yamada H, Ishikawa T, Maeda N, Goshima F, Nishiyama Y, et al. A regulatory role of interleukin 15 in wound healing and mucosal infection in mice. J Leukoc Biol. 2008;83:165-72 pubmed
    ..Taken together, overexpression of IL-15 may stimulate IEL to produce TGF-beta1, promoting wound healing but impeding protection against genital HSV-2 infection. ..
  21. Kim H, Hwang K, Kang I. Dual roles of IL-15 in maintaining IL-7RalphalowCCR7- memory CD8+ T cells in humans via recovering the phosphatidylinositol 3-kinase/AKT pathway. J Immunol. 2007;179:6734-40 pubmed
    ..Moreover, IL-15 can be useful in reviving impaired proliferative function of such memory CD8(+) T cells with effector functions against infections and tumors via rescuing the PI3K/AKT pathway. ..
  22. Zeng R, Spolski R, Casas E, Zhu W, Levy D, Leonard W. The molecular basis of IL-21-mediated proliferation. Blood. 2007;109:4135-42 pubmed
    ..Collectively, these data indicate the involvement of the Jak-STAT, MAPK, and PI3K pathways in IL-21 signaling. ..
  23. French A, Holroyd E, Yang L, Kim S, Yokoyama W. IL-18 acts synergistically with IL-15 in stimulating natural killer cell proliferation. Cytokine. 2006;35:229-34 pubmed
    ..This raises the possibility that IL-18 may act synergistically with IL-15 in driving pathogen-induced NK cell proliferation in addition to its contribution in enhancing IL-12 stimulation of NK cell IFNgamma production. ..
  24. Stoklasek T, Schluns K, Lefrancois L. Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol. 2006;177:6072-80 pubmed
    ..These findings hold significant importance for the use of IL-15 as a potential adjuvant/therapeutic and inducer of homeostatic proliferation, without the necessity for prior immunodepletion. ..
  25. Chiu W, Fann M, Weng N. Generation and growth of CD28nullCD8+ memory T cells mediated by IL-15 and its induced cytokines. J Immunol. 2006;177:7802-10 pubmed
  26. Godlove J, Chiu W, Weng N. Gene expression and generation of CD28-CD8 T cells mediated by interleukin 15. Exp Gerontol. 2007;42:412-5 pubmed CD28(-)) cells and the growth of CD28(+) and CD28(-)CD8 memory T cells in response to homeostatic cytokine interleukin 15 (IL-15)...
  27. Chiossone L, Vitale C, Cottalasso F, Moretti S, Azzarone B, Moretta L, et al. Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell function: evidence for different susceptibility of IL-2- versus IL-15-activated NK cells. Blood. 2007;109:3767-75 pubmed
    ..Our study suggests a different ability of IL-15-cultured NK cells to survive to steroid treatment, thus offering interesting clues for a correct NK-cell cytokine conditioning in adoptive immunotherapy. ..
  28. Hryniewicz A, Price D, Moniuszko M, Boasso A, Edghill Spano Y, West S, et al. Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques. J Immunol. 2007;178:3492-504 pubmed
    ..These results underscore the importance of testing immunomodulatory approaches in vivo to assess potential risks and benefits for HIV-1-infected individuals. ..
  29. Hsu C, Jones S, Cohen C, Zheng Z, Kerstann K, Zhou J, et al. Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene. Blood. 2007;109:5168-77 pubmed
    ..It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation. ..
  30. Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity. 2007;26:503-17 pubmed
    ..Our data define a unique in vivo role of DCs for the priming of NK cells, revealing a striking and previously unappreciated homology to T lymphocytes of the adaptive immune system. ..
  31. Dubsky P, Saito H, Leogier M, Dantin C, Connolly J, Banchereau J, et al. IL-15-induced human DC efficiently prime melanoma-specific naive CD8+ T cells to differentiate into CTL. Eur J Immunol. 2007;37:1678-90 pubmed
    ..Therefore, membrane-bound IL-15 might contribute to enhanced priming by IL15-DC. Thus, IL-15 induces myeloid DC that are efficient in priming and maturation of melanoma antigen-specific CTL. ..
  32. Romagnani C, Juelke K, Falco M, Morandi B, D Agostino A, Costa R, et al. CD56brightCD16- killer Ig-like receptor- NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation. J Immunol. 2007;178:4947-55 pubmed
  33. Waldmann T. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol. 2006;6:595-601 pubmed
    ..As discussed in this Review, the biology of these cytokines will affect the development of novel therapies for malignancy and autoimmune diseases, as well as the design of vaccines against infectious diseases. ..
  34. Leon A, Garrote J, Blanco Quiros A, Calvo C, Fernández Salazar L, del Villar A, et al. Interleukin 18 maintains a long-standing inflammation in coeliac disease patients. Clin Exp Immunol. 2006;146:479-85 pubmed
  35. Sato N, Patel H, Waldmann T, Tagaya Y. The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells. Proc Natl Acad Sci U S A. 2007;104:588-93 pubmed
  36. Nakazato K, Yamada H, Yajima T, Kagimoto Y, Kuwano H, Yoshikai Y. Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRgammadelta intestinal intraepithelial T lymphocytes in IL-15-deficient mice. J Immunol. 2007;178:757-64 pubmed
  37. Bernardo D, Garrote J, Fernández Salazar L, Riestra S, Arranz E. Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut. 2007;56:889-90 pubmed
  38. Purton J, Tan J, Rubinstein M, Kim D, Sprent J, Surh C. Antiviral CD4+ memory T cells are IL-15 dependent. J Exp Med. 2007;204:951-61 pubmed
    ..Therefore, under normal physiological conditions, homeostasis of CD8(+) and CD4(+) memory cells is quite similar and involves IL-15 and IL-7. ..
  39. Ramsborg C, Papoutsakis E. Global transcriptional analysis delineates the differential inflammatory response interleukin-15 elicits from cultured human T cells. Exp Hematol. 2007;35:454-464 pubmed
    b>Interleukin 15 (IL)-15 controls proliferation and survival of T cells, but its effects and the underlying cellular regulation are not well understood. Previous studies have focused on its effects on short-term T-cell cultures...
  40. Benahmed M, Meresse B, Arnulf B, Barbe U, Mention J, Verkarre V, et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology. 2007;132:994-1008 pubmed
  41. Mallidi T, Craig L, Schloemann S, Riley J. Murine endometrial and decidual NK1.1+ natural killer cells display a B220+CD11c+ cell surface phenotype. Biol Reprod. 2009;81:310-8 pubmed publisher
    ..B220(hi)ICOS(+) dNK cell surface phenotype when cultured in vitro in the presence of uterine cells and murine interleukin 15. Thus, the cell surface profiles generated for both NK1...
  42. Min H, Won H, Kim Y, Sung S, Byun M, Hwang J, et al. Suppression of Th2-driven, allergen-induced airway inflammation by sauchinone. Biochem Biophys Res Commun. 2009;385:204-9 pubmed publisher
  43. Larrea E, Aldabe R, Gonzalez I, Segura V, Sarobe P, Echeverria I, et al. Oncostatin M enhances the antiviral effects of type I interferon and activates immunostimulatory functions in liver epithelial cells. J Virol. 2009;83:3298-311 pubmed publisher
    ..In conclusion, OSM enhances the antiviral effects of type I interferon and cooperates with it in the induction of adaptive immune responses to pathogens. These findings may have therapeutic implications. ..
  44. Beuneu H, Deguine J, Breart B, Mandelboim O, Di Santo J, Bousso P. Dynamic behavior of NK cells during activation in lymph nodes. Blood. 2009;114:3227-34 pubmed publisher
    ..That NK cells become activated while remaining motile may constitute an efficient strategy for sampling local concentrations of cytokines around DCs in secondary lymphoid tissues. ..
  45. Umehara T, Udagawa J, Takamura K, Kimura M, Ishimitsu R, Kiyono H, et al. Role of interleukin-15 in the development of mouse olfactory nerve. Congenit Anom (Kyoto). 2009;49:253-7 pubmed publisher
    ..Adult IL-15R alpha knockout mice had fewer mature olfactory neurons and proliferating cells than wild-type. Our results suggest that IL-15 plays an important role in regulating cell proliferation in olfactory neurogenesis. ..
  46. Ota N, Takase M, Uchiyama H, Olsen S, Kanagawa O. No requirement of trans presentations of IL-15 for human CD8 T cell proliferation. J Immunol. 2010;185:6041-8 pubmed publisher
    ..Therefore, careful study of the human immune system, rather than extrapolation from the murine model, is necessary to achieve more complete understanding of memory CD8 T cell development in humans. ..
  47. Lin J, Spolski R, Leonard W. Critical role for Rsk2 in T-lymphocyte activation. Blood. 2008;111:525-33 pubmed
    ..These results indicate an essential nonredundant role of Rsk2 in T-cell activation. ..
  48. Giron Michel J, Menard F, Negrini S, Devocelle A, Azzarone B, Besson C. EBV-associated mononucleosis does not induce long-term global deficit in T-cell responsiveness to IL-15. Blood. 2009;113:4541-7 pubmed publisher
  49. Watkins S, Li B, Richardson K, Head K, Egilmez N, Zeng Q, et al. Rapid release of cytoplasmic IL-15 from tumor-associated macrophages is an initial and critical event in IL-12-initiated tumor regression. Eur J Immunol. 2009;39:2126-35 pubmed publisher
    ..In this context, the functional plasticity and pro-immunogenic potential of TAM may constitute a significant and unappreciated target in existing cytokine therapies. ..
  50. Ledee N, Dubanchet S, Oger P, Meynant C, Lombroso R, Ville Y, et al. Uterine receptivity and cytokines: new concepts and new applications. Gynecol Obstet Invest. 2007;64:138-43 pubmed
  51. Rafei M, Hsieh J, Zehntner S, Li M, Forner K, Birman E, et al. A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nat Med. 2009;15:1038-45 pubmed publisher
    ..We propose that autologous GIFT15 B(reg) cells may serve as a new treatment for autoimmune ailments. ..
  52. Decot V, Voillard L, Latger Cannard V, Aïssi Rothé L, Perrier P, Stoltz J, et al. Natural-killer cell amplification for adoptive leukemia relapse immunotherapy: comparison of three cytokines, IL-2, IL-15, or IL-7 and impact on NKG2D, KIR2DL1, and KIR2DL2 expression. Exp Hematol. 2010;38:351-62 pubmed publisher
    ..In our study, 10 ng/mL IL-2 or 50 ng/mL IL-15 were the optimal concentrations for expansion and were equivalent in significantly enhancing cytotoxicity and modifying NK-cell receptor expression patterns. ..