Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design

Nature Reviews Immunology volume 6, pages 595–601 (2006)Cite this article

Key Points

  • Interleukin-2 (IL-2) and IL-15 have both similar and contrasting functional roles in the life and death of lymphocytes.

  • The heterotrimeric receptors for these cytokines have two subunits in common: IL-2/15Rβ (also known as the IL-2 receptor β-chain (IL-2Rβ) and IL-15Rβ); and the common cytokine-receptor γ-chain (γc). The two cytokine receptors also have distinct α-subunits.

  • In many adaptive immune responses, IL-2 and IL-15 have distinct, and often competing, actions. IL-2 has a role in activation-induced cell death and in maintenance of regulatory T cells. In this way, it is involved in the elimination of self-reactive T cells, which if left unregulated could lead to the development of autoimmune diseases. By contrast, IL-15 is pivotal in the maintenance of long-lasting, high-avidity CD8+ memory T cells that are involved in the elimination of invading pathogens, thereby protecting the host against infection.

  • IL-2 is a secreted cytokine and binds pre-formed heterotrimeric receptors on the surface of activated cells. By contrast, IL-15 is mainly membrane bound, and it induces signalling in the context of cell–cell contact, at the immunological synapse. The unique subunit of the IL-15R, IL-15Rα, presents IL-15 in trans to neighbouring natural killer (NK) cells and CD8+ T cells.

  • IL-15 activates T cells and NK cells and has a role in persistence of CD8+ memory T cells. It therefore might be better than IL-2 for the treatment of cancer and as a component of molecular vaccines against infectious diseases.

  • Because IL-15 activates tumour-necrosis-factor expression and facilitates memory CD8+ T-cell maintenance, dysregulation of IL-15 is associated with a range of autoimmune inflammatory diseases. Therapeutic strategies that inhibit the actions of IL-15 are being developed for the treatment of T-cell-mediated autoimmune inflammatory diseases.

Abstract

Interleukin-2 and interleukin-15 have pivotal roles in the control of the life and death of lymphocytes. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of interleukin-2 is in the elimination of self-reactive T cells to prevent autoimmunity. By contrast, interleukin-15 is dedicated to the prolonged maintenance of memory T-cell responses to invading pathogens. 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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The structure and signalling pathways of the common cytokine-receptor γ-chain family of receptors.
Figure 2: The mode of interaction of interleukin-2 and interleukin-15 with the subunits of their receptors.
Figure 3: The interleukin-15 receptor α-chain presents interleukin-15 in trans to neighbouring natural killer cells and CD8+ T cells.

Similar content being viewed by others

References

  1. Sugamura, K. et al. The interleukin-2 receptor γ chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu. Rev. Immunol. 14, 179–205 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Noguchi, M. et al. Interleukin-2 receptor γ chain: a functional component of the interleukin-7 receptor. Science 262, 1877–1880 (1993).

    Article  CAS  PubMed  Google Scholar 

  3. Waldmann, T. A., Dubois, S. & Tagaya, Y. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 14, 105–110 (2001). This Review provides an analysis of the similarities and differences in the functions of IL-2 and IL-15, as well as the mechanisms that underlie the distinct functions.

    CAS  PubMed  Google Scholar 

  4. Waldmann, T. A. & Tagaya, Y. The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu. Rev. Immunol. 17, 19–49 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Fehniger, T. A. & Caligiuri, M. A. Interleukin 15: biology and relevance to human disease. Blood 97, 14–32 (2001). This is an excellent review of IL-15 biology. It discusses the disorders of IL-15 in human diseases and considers the implications of these abnormalities for immunotherapy.

    Article  CAS  PubMed  Google Scholar 

  6. Bamford, R. N. et al. The interleukin (IL) 2 receptor β chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc. Natl Acad. Sci. USA 91, 4940–4944 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Grabstein, K. H. et al. Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor. Science 264, 965–968 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. Giri, J. G. et al. Identification and cloning of a novel IL-15 binding protein that is structurally related to the α chain of the IL-2 receptor. EMBO J. 14, 3654–3663 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Waldmann, T. A. The interleukin-2 receptor. J. Biol. Chem. 266, 2681–2684 (1991).

    CAS  PubMed  Google Scholar 

  10. Taniguchi, T. & Minami, Y. The IL-2/IL-2 receptor system: a current overview. Cell 73, 5–8 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Miyazaki, T. et al. Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc and lck cooperate in hematopoietic cell proliferation. Cell 81, 223–231 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, X., Sun, S., Hwang, I., Tough, D. F. & Sprent, J. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8, 591–599 (1998). This was the first report to indicate that IL-15 has an important role in stimulation of the proliferation of CD8+CD44hi memory T cells.

    Article  CAS  PubMed  Google Scholar 

  13. Ku, C. C., Murakami, M., Sakamoto, A., Kappler, J. & Marrack, P. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 288, 675–678 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Marks-Konczalik, J. et al. IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc. Natl Acad. Sci. USA 97, 11445–11450 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fehniger, T. A., Cooper, M. A. & Caligiuri, M. A. Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev. 13, 169–183 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Carson, W. E. et al. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J. Clin. Invest. 99, 937–943 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lenardo, M. J. Fas and the art of lymphocyte maintenance. J. Exp. Med. 183, 721–724 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Fontenot, J. D., Rassmussen, J. P., Gavin, M. A. & Rudensky, A. Y. A function for interleukin-2 in FOXP3-expressing regulatory T cells. Nature Immunol. 6, 1142–1151 (2005).

    Article  CAS  Google Scholar 

  19. D'Cruz, L. M. & Klein, L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nature Immunol. 6, 1152–1159 (2005).

    Article  CAS  Google Scholar 

  20. Maloy, K. J. & Powrie, F. Fueling regulation: IL-2 keeps CD4+ Treg cells fit. Nature Immunol. 6, 1071–1072 (2005).

    Article  CAS  Google Scholar 

  21. Schluns, K. S., Klonowski, K. D. & Lefrancois, L. Transregulation of memory CD8 T-cell proliferation by IL-15Rα+ bone marrow-derived cells. Blood 103, 988–994 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Becker, T. C. et al. Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J. Exp. Med. 195, 1541–1548 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rosenberg, S. A. Interleukin-2 and the development of immunotherapy for the treatment of patients with cancer. Cancer J. Sci. Am. 6, S2–S7 (2000).

    PubMed  Google Scholar 

  24. Waldmann, T. A. et al. The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. Blood 82, 1701–1712 (1993).

    CAS  PubMed  Google Scholar 

  25. Morris, J. C. et al. Preclinical and Phase I clinical trial of blockade of IL-15 using Mikβ1 monoclonal antibody in T cell large granular lymphocyte leukemia. Proc. Natl Acad. Sci. USA 103, 401–406 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Waldmann, T. A., Dubois, S., Muller, J., Goldman, C. & Damjanovich, S. in Biophysical Aspects of Transmembrane Signaling (ed. Damjanovich, S.) 97–121 (Springer, Heidelberg, 2005).

    Book  Google Scholar 

  27. Schorle, H., Holtschke, T., Hunig, T., Schimpl, A. & Horak, I. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352, 621–624 (1991).

    Article  CAS  PubMed  Google Scholar 

  28. Sadlack, B. et al. Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur. J. Immunol. 24, 281–284 (1994).

    Article  CAS  PubMed  Google Scholar 

  29. Lodolce, J. P. et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9, 669–676 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Kennedy, M. K. et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J. Exp. Med. 191, 771–780 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kishimoto, T. et al. (eds) Leukocyte typing VI. White Cell Differentiation Antigens (Garland, New York, 1997).

    Google Scholar 

  32. Dubois, S. et al. Distinct pathways involving the FK506-binding proteins 12 and 12.6 underlie IL-2 versus IL-15-mediated proliferation of cells. Proc. Natl Acad. Sci. USA 100, 14169–14174 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bulfone-Paus, S. et al. Death deflected: IL-15 inhibits TNF-α-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Rα chain. FASEB J. 13, 1575–1585 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Damjanovich, S. et al. Preassembly of interleukin 2 (IL-2) receptor subunits on resting Kit 225 K6 T cells and their modulation by IL-2, IL-7, and IL-15: a fluorescence resonance energy transfer study. Proc. Natl Acad. Sci. USA 94, 13134–13139 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Dubois, S., Mariner, J., Waldmann, T. A. & Tagaya, Y. IL-15Rα recycles and presents IL-15 in trans to neighboring cells. Immunity 17, 537–547 (2002). This was the first study to show that IL-15 bound to IL-15Rα recycles through endosomal vesicles and that IL-15Rα on the surface of monocytes and DCs presents IL-15 in trans to NK cells and CD8+CD44hi memory T cells. In this way, the study showed that IL-15 has an important role in the generation, persistence and differentiation of NK cells and CD8+CD44hi memory T cells.

    Article  CAS  PubMed  Google Scholar 

  36. Lodolce, J. P., Burkett, P. R., Boone, D. L., Chien, M. & Ma, A. T-cell-independent interleukin 15Rα signals are required for bystander proliferation. J. Exp. Med. 194, 1187–1194 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rosenberg, S. A. et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin-2. JAMA 271, 907–913 (1994).

    Article  CAS  PubMed  Google Scholar 

  38. Munger, W. et al. Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2. Cell. Immunol. 165, 289–293 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Evans, R., Fuller, J. A., Christianson, G., Krupke, D. M. & Troutt, A. B. IL-15 mediates anti-tumor effects after cyclophosphamide injection of tumor-bearing mice and enhances adoptive immunotherapy: the potential role of NK cell subpopulations. Cell. Immunol. 179, 66–73 (1997).

    Article  CAS  PubMed  Google Scholar 

  40. Yajima, T. et al. Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T-cell response. Int. J. Cancer 99, 573–578 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Kobayashi, H. et al. Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 105, 721–727 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Oh, S., Berzofsky, J. A., Burke, D. S., Waldmann, T. A. & Perera, L. P. Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity. Proc. Natl Acad. Sci. USA 100, 3392–3397 (2003). In this study, vaccines that express IL-15 were found to induce long-lasting CD8+ T-cell-mediated immunity, whereas vaccines incorporating IL-2 elicited short-lived immunity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Oh, S., Perera, L. P., Burke, D. S., Waldmann, T. A. & Berzofsky, J. A. IL-15/IL-15Rα-mediated avidity maturation of memory CD8+ T cells. Proc. Natl Acad. Sci. USA 101, 15154–15159 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kutzler, M. A. et al. Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J. Immunol. 175, 112–123 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Nashan, B. et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet 350, 1193–1198 (1997).

    Article  CAS  PubMed  Google Scholar 

  46. Kirkman, R. L. et al. A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation. Transplantation 51, 107–113 (1991).

    Article  CAS  PubMed  Google Scholar 

  47. Vincenti, F. et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N. Engl. J. Med. 338, 161–165 (1998). This report of a Phase III clinical trial of daclizumab shows that it is effective for the reduction of acute renal-allograft rejection episodes in patients receiving a human renal transplant. On the basis of this study, the FDA approved daclizumab for use in renal organ-transplantation protocols.

    Article  CAS  PubMed  Google Scholar 

  48. Waldmann, T. A. et al. Radioimmunotherapy of interleukin-2Rα-expressing adult T-cell leukemia with yttrium-90-labeled anti-Tac. Blood 86, 4063–4075 (1995).

    CAS  PubMed  Google Scholar 

  49. Nussenblatt, R. B. et al. Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a Phase I/II clinical trial. Proc. Natl Acad. Sci. USA 96, 7462–7466 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bielekova, B. et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon β. Proc. Natl Acad. Sci. USA 101, 8705–8708 (2004). This paper shows that treatment with daclizumab leads to a 78% reduction in new contrast-enhancing lesions in patients with multiple sclerosis who have failed to respond to treatment with IFNβ.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Waldmann, T. A. et al. Functional and phenotypic comparison of human T cell leukemia/lymphoma virus positive adult T cell leukemia with human T cell leukemia/lymphoma virus negative Sezary leukemia, and their distinction using anti-Tac. Monoclonal antibody identifying the human receptor for T cell growth factor. J. Clin. Invest. 73, 1711–1718 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Waldmann, T. A. The meandering 45-year odyssey of a clinical immunologist. Annu. Rev. Immunol. 21, 1–27 (2002).

    Article  Google Scholar 

  53. McInnes, I. B., Leung, B. P., Sturrock, R. D., Field, M. & Liew, F. Y. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-α production in rheumatoid arthritis. Nature Med. 3, 189–195 (1997). This study found that IL-15 effectively induces TNF production in patients with rheumatoid arthritis, through a process that requires the interaction of synovial cells and T cells.

    Article  Google Scholar 

  54. Azimi, N., Nagai, M., Jacobson, S. & Waldmann, T. A. IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients. Proc. Natl Acad. Sci. USA 98, 14559–14564 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ruchatz, H., Leung, B. P., Wei, X. Q., McInnes, I. B. & Liew, F. Y. Soluble IL-15 receptor α-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology. J. Immunol. 160, 5654–5660 (1998).

    CAS  PubMed  Google Scholar 

  56. Kim, Y. S. et al. Targeting the IL-15 receptor with an antagonist IL-15 mutant/Fcγ2a protein blocks delayed-type hypersensitivity. J. Immunol. 160, 5742–5748 (1998).

    CAS  PubMed  Google Scholar 

  57. Baslund, B. et al. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum. 52, 2686–2692 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Villadsen, L. S. et al. Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model. J. Clin. Invest. 112, 1571–1580 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mention, J. J. et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 125, 730–745 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Harada, S. et al. Production of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum. 42, 1508–1516 (1999).

    Article  CAS  PubMed  Google Scholar 

  61. Oppenheimer-Marks, N., Brezinschek, R. I., Mohamadzadeh, M., Vita, R. & Lipsky, P. E. Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells in vitro and in the SCID mouse–human rheumatoid arthritis model in vivo. J. Clin. Invest. 101, 1261–1272 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Losy, J., Niezgoda, A. & Zaremba, J. IL-15 is elevated in sera of patients with relapsing–remitting multiple sclerosis. Folia Neuropathol. 40, 151–153 (2002).

    PubMed  Google Scholar 

  63. Meresse, B. et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357–366 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Feldmann, M., Brennan, F. M. & Maini, R. N. Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14, 397–440 (1996).

    Article  CAS  PubMed  Google Scholar 

  65. Guex-Crosier, Y. et al. Humanized antibodies against the α-chain of the IL-2 receptor and against the β-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases. J. Immunol. 158, 452–458 (1997).

    CAS  PubMed  Google Scholar 

  66. Hakimi, J. et al. Humanized Mikβ1, a humanized antibody to the IL-2 receptor β-chain that acts synergistically with humanized anti-TAC. J. Immunol. 151, 1075–1085 (1993).

    CAS  PubMed  Google Scholar 

  67. Tinubu, S. A. et al. Humanized antibody directed to the IL-2 receptor β-chain prolongs primate cardiac allograft survival. J. Immunol. 153, 4330–4338 (1994).

    CAS  PubMed  Google Scholar 

  68. Leonard, W. J. in Cytokine Reference Vol. 2 (eds Oppenheim, J. J. & Feldmann, M.) 1439–1457 (Academic, San Diego, 2001).

    Google Scholar 

Download references

Acknowledgements

This research was supported by the Intramural Program of the National Cancer Institute, National Institutes of Health (USA).

Author information

Authors and Affiliations

  1. Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Thomas A. Waldmann

Authors
  1. Thomas A. Waldmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design Nature Reviews Immunology 6, 595–601 (2006); doi:10.1038/nri1901

Together with the US government, Thomas Waldmann holds patent number 5,833,983, entitled Interleukin-2 receptor (IL-2Rβ) and application thereof. This patent provides royalty payments.

Glossary

Activation-induced cell death

(AICD). A process by which fully activated T cells undergo programmed cell death through engagement of cell-surface-expressed death receptors such as CD95 (also known as FAS) or the tumour-necrosis-factor receptor.

CD4+CD25+ regulatory T cell

(TReg cell). A specialized type of CD4+ T cell that can suppress the responses of other T cells. These cells provide a crucial mechanism for the maintenance of peripheral self-tolerance and are characterized by expression of the α-chain of the interleukin-2 receptor (also known as CD25) and the transcription factor forkhead box P3 (FOXP3).

Intestinal intraepithelial lymphocyte

A T cell that resides in the basolateral side of the intestinal epithelium. These cells express either an αβ-T-cell receptor (TCR) or a γδ-TCR, as well as a CD8αα homodimer. This is in contrast to most conventional CD8+ T cells, which express a CD8αβ heterodimer. CD8αα is a ligand for the non-classical MHC class I molecule thymus leukaemia antigen (TL), which is expressed by the intestinal epithelium.

Trans-presentation

A process by which the α-chain of the interleukin-15 (IL-15) receptor (IL-15Rα) presents active IL-15 in trans to opposing cells expressing a complex (with an intermediate affinity for IL-15) that contains the β-chain IL-2/15Rβ and the common cytokine-receptor γ-chain (γc), thereby transducing a signal.

Fluorescence resonance energy transfer

(FRET). A technique that is used to measure protein–protein interactions either by microscopy or flow cytometry. Proteins fused to cyan, yellow or red fluorescent proteins are expressed and assessed for interaction by measuring the energy transfer between fluorophores. Such transfer can only occur if proteins physically interact.

Immunological synapse

A region that can form between two cells of the immune system in close contact. The name derives from similarities to the synapses that occur in the nervous system. The immunological synapse refers to the interaction between a T cell or natural killer cell and an antigen-presenting cell. This interface involves adhesion molecules, as well as antigen receptors and cytokine receptors.

Delayed-type hypersensitivity

A cellular immune response to antigen that develops over 24–72 hours. It involves the infiltration of T cells and monocytes, and it depends on the production of T-helper-1 cytokines.

Collagen-induced arthritis

An experimental model of rheumatoid arthritis. Arthritis is induced by immunization of susceptible animals with type II collagen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waldmann, T. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 6, 595–601 (2006). https://doi.org/10.1038/nri1901

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri1901

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing