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Interleukin-2 biology and immunology

  • Giorgio Parmiani
  • Carlo Gambacorti-Passerini
Chapter

Abstract

Interleukin-2 (IL-2), formerly known as T Cell growth factor, is a 15 KD inducible glycoprotein synthesized by T lymphocytes and plays a pivotal role in the lymphocyte activation network. In particular, IL-2 represents the most important growth factor for T lymphocytes and NK cells.

Keywords

Natural Killer Cell Chronic Lymphocytic Leukemia Mitogenic Effect Large Granular Lymphocyte Natural Killer Cell Stimulatory Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Shows T, Eddy R, Haley L, et al. Interleukin 2 (IL2) is assigned to human chromosome 4. Som Cell Mol Genet 1984; 10: 315–20.CrossRefGoogle Scholar
  2. 2.
    Wang A, Lu S-D, Mark DF. Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues. Science 1984; 224: 1431–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Robb RJ, Kutny RM, Panico M, et al. Amino acid sequence and post-translational modifications of human interleukin-2. Proc Natl Acad Sci USA 1984; 81: 8486–91.CrossRefGoogle Scholar
  4. 4.
    Taniguchi M, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature 1983; 302: 305–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Matsui H, Fujita T, Nishi-Takaoka C, et al. Molecular cloning and expression of the human interleukin-2 gene. In: Pick E, editor. Lymphokine, Vol. 12. New York: Academic Press, 1985: 1–12.Google Scholar
  6. 6.
    Brandhuber BJ, Boone T, Kenney WC, McKay DB. Three-Dimensional Structure of Interleukin-2. Science 1987; 238: 1707–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Kuo L, Robb RJ. Structure-function relationships for the IL 2-receptor system. J Immunol 1986; 137: 1538–43.PubMedGoogle Scholar
  8. 8.
    Altman A, Cardenas JM, Houghten RA, et al. Antibodies of predetermined specificity against chemically sinthetized peptides of human interleukin 2. Proc Natl Acad Sci USA 1984; 81: 2176–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Honjo T. Shared patterns in receptors. Curr Opinion Biol 1991; 1: 201–3.CrossRefGoogle Scholar
  10. 10.
    Smith KA. Interleukin-2: inception, impact and implications. Science 1988; 240: 1169–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Phillips JH, Takeshita T, Sugamura K, Lanier LL. Activation of natural killer cells via the p75 interleukin 2 receptor. J Exp Med 1989; 170: 291–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Saragovi H, Malek T. Proc Natl Acad Sci USA 1990; 87: 11–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Saito Y, Tada H, Sabe H, Honjo T. Biochemical evidence for a third chain of the interleukin 2 receptor. J Biol Chem 1991; 266: 22186–91.PubMedGoogle Scholar
  14. 14.
    Gambacorti-Passerini C, Rovelli F, Ghezzi R, et al. Serum CD25 levels in patients treated with rIL2 and LAK. Correlation with in vivo immune activation. J Immunol Res 1990; 2: 19–24.Google Scholar
  15. 15.
    Asao H, Takeshita T, Nakamura M, et al. Interleukin 2 (IL-2) induced tyrosine phosphorilation of IL-2 receptor p75. J Exp Med 1990; 171: 637–44.PubMedCrossRefGoogle Scholar
  16. 16.
    Sharon M, Gnarra JR, Leonard WJ. The ß-chain of the IL-2 receptor (p70) is tyrosine-phosphorilated on YT and HUT-102B2 cells. J Immunol 1989; 143, 2530–3.PubMedGoogle Scholar
  17. 17.
    June CH, Fletcher MC, Ledbetter JA, et al. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. Proc Natl Acad Sci USA 1990; 87: 7722–26.PubMedCrossRefGoogle Scholar
  18. 18.
    Horak ID, Gress RE, Lucas PJ, et al. T-lymphocyte interleukin-2 dependent tyrosine protein kinase signal transduction involves the activation of p561ck. Proc Natl Acad Sci USA 1991; 88: 1996–2000.PubMedCrossRefGoogle Scholar
  19. 19.
    Turner B, Rapp U, Greene M, et al. Interleukin 2 induces tyrosine phosphorilation and activation of p72–74 Raf-1 kinase in a T-cell line. Proc Natl Acad Sci USA 1991; 88: 1227–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Morrison D, Kaplan D, Escobedo J, et al. Direct activation of the serine/threonine kinase activity of Raf-1 through tyrosine phosphorilation by the PDGF ß-receptor. Cell 1989; 58: 649–57.PubMedCrossRefGoogle Scholar
  21. 21.
    Mond JJ, Thompson C, Finkelman FD, et al. Affinity-purified interleukin 2 induces proliferation of large but not small B cells. Proc Natl Acad Sci USA 1985; 82: 1518–21.PubMedCrossRefGoogle Scholar
  22. 22.
    Herrmann F, Cannistra SA, Levine H, Griffin JD. Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocyte cells. J Exp Med 1985; 162: 1111–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Benveniste EN, Merrill JE. Stimulation of oligodendroglial proliferation and maturation by interleukin-2. Nature 1986; 321:610–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Steiner G, Tschachler E, Tani M, et al. Interleukin-2 receptors on cultured murine epidermal Langherans cells. J Immunol 1986; 137: 155–9.PubMedGoogle Scholar
  25. 25.
    Benveniste EN, Herman PK, Whitaker JN. Myelin basic protein-specific RNA levels in interleukin-2-stimulated oligodendrocytes. J Neurochem 1987; 49: 1274–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Plaisance S, Rubinstein E, Alileche A, et al. Human melanoma cells express an IL-2R, which is involved in the modulation of the ICAM-1 protein. Proc. Am Ass Cancer Res 1991; 31: 240.Google Scholar
  27. 27.
    Malkovska V, Murphy J, Hudson L, Bevan D. Direct effect of interleukin-2 on chronic lymphocytic leukemia B cell function and morphology. Clin Exp Immunol 1987; 68: 677–84.PubMedGoogle Scholar
  28. 28.
    Yamamoto S, Hattori T, Matsuoka M, et al. Induction of Tac antigen and proliferation of myeloid leukemic cells by ATL-derived factor: comparison with other agents that promote differentiation of human myeloid or monocytic leukemic cells. Blood 1986; 67: 1713–20.Google Scholar
  29. 29.
    Estrov Z, Freedman MH. Growth requirements for human acute lymphoblastic leukemia cells: refinement of a clonogenic assay. Cancer Res 1988; 48: 2372–6.Google Scholar
  30. 30.
    Lotze MT, Matory YL, Ettinghausen SE, et al. In vivo administration of purified human interleukin 2. II. Half-life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant interleukin-2. J Immunol 1985; 135: 2865–75.PubMedGoogle Scholar
  31. 31.
    Meuer SC, Hussey R, Cantrell DA, et al. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci USA 1984; 81: 1509–13.PubMedCrossRefGoogle Scholar
  32. 32.
    Dianzani U, Zarcone D, Pistoia V, et al. CD8 + /CDllb+ peripheral blood T lymphocytes contain lymphokine-activated killer cell precursors. Eur J Immunol 1989; 19: 1037–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Silvennoinen O, Vakkila J, Hurme M. Accessory cells, dendritic cells, or monocytes are required for the lymphokine-activated killer cell induction from resting T cells but not from natural killer cell precursors. J Immunol 1988; 141: 1404–9.PubMedGoogle Scholar
  34. 34.
    Lenardo MJ. Interleukin-2 programs mouse αß T lymphocytes for apoptosis. Nature 1991; 353:858–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Perussia B. Lymphokine-activated killer cells, natural killer cells and cytokines. Curr Opin Immunol 1991; 3: 49–55.PubMedCrossRefGoogle Scholar
  36. 36.
    London P, Perussia B, Trinchieri G. Induction of proliferation in vitro of resting human natural killer cells: IL-2 induces into cell cycle most peripheral blood NK cells, but only a minor subset of low density T cells. J Immunol 1986; 137: 3845–54.PubMedGoogle Scholar
  37. 37.
    Tsudo M, Goldman CK, Bongiovanni KF, et al. The p75 peptide is the receptor for interleukin-2 expressed on a large granular lymphocytes and is responsible for the interleukin-2 activation of these cells. Proc Natl Acad Sci USA 1987; 84: 5394–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Kobayashi M, Fitz L, Ryan M, et al. Identification and purification of natural killer cell stimulatory factor (NKSF). J Exp Med 1989; 170: 827–46.PubMedCrossRefGoogle Scholar
  39. 39.
    Smyth MJ, Ortaldo JR. Comparison of the effect of IL-2 and IL-6 on the lytic activity of purified human peripheral blood large granular lymphocytes. J Immunol 1991; 146: 1380–4.PubMedGoogle Scholar
  40. 40.
    Naume B, Espevik T. Effects of IL-7 and IL-2 on highly enriched CD56 4-natural killer cells. A comparative study. J Immunol 1991; 147: 2208–14.PubMedGoogle Scholar
  41. 41.
    Vaage JT, Reynolds CW, Reynolds D, et al. The proliferation and life-span of rat large granular lymphocytes: effects of cytokines. Eur J Immunol 1989; 19: 1895–1902.PubMedCrossRefGoogle Scholar
  42. 42.
    Spits H, Yssel H, Pallard X, et al. IL-4 inhibits IL-2 mediated induction of human lymphokine-activated killer cells, but not the generation of antigen-specific cytotoxic T lymphocytes in mixed leukocyte cultures. J Immunol 1988; 141: 29–36.PubMedGoogle Scholar
  43. 43.
    Owen-Schaub LB, Crump WL III, Morin GI, Grimm EA. Regulation of lymphocyte tumor-necrosis factor receptors by IL-2. J Immunol 1989; 143: 2236–41.PubMedGoogle Scholar
  44. 44.
    Naume B, Shalaby R, Lesslauer W, Espevik T. Involvement of the 55-and 75-KDa tumor necrosis factor receptors in the generation of lymphokine-activated killer cell activity and proliferation of natural killer cells. J Immunol 1991; 146: 3045–8.PubMedGoogle Scholar
  45. 45.
    Chen W, Reese VA, Cheever MA. Adoptively transferred antigen-specific T cells can be grown and maintained in large numbers in vivo for extended periods of time by intermittent restimulation with specific antigen plus IL-2. J Immunol 1990; 144: 3659–66.PubMedGoogle Scholar
  46. 46.
    Rodolfo M, Bassi C, Salvi C, Parmiani G. Therapeutic use of a long-term cytotoxic T cell line recognizing a common tumour-associated antigen: the pattern of in vitro reactivity predicts the in vivo effect on different tumours. Cancer Immunol Immunother 1991; 34: 53–62.PubMedCrossRefGoogle Scholar
  47. 47.
    Biron CA, Young HA, Kasauani NT. Interleukin-2-induced proliferation of murine natural killer cells in vivo. J Exp Med 1990; 171: 173–88.PubMedCrossRefGoogle Scholar
  48. 48.
    Ellis TM, Creekmore SP, McMannis JD, et al. Appearance and phenotypic characterization of circulating Leu 19+ cells in cancer patients receiving recombinant interleukin 2. Cancer Res 1988; 48: 6597–6602.PubMedGoogle Scholar
  49. 49.
    Gambacorti-Passerini C, Radrizzani M, Marolda R, et al. In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2. Int J Cancer 1988; 41:700–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Schorle H, Holtschke T, Hünig T, et al. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 1991; 352: 621–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Swain SL. Lymphokine and the immune response: the central role of interleukin-2. Curr Opin Immunol 1991; 3: 304–10.PubMedCrossRefGoogle Scholar
  52. 52.
    Kishimoto T. The biology of interleukin-6. Blood 1989; 74: 1–10.PubMedGoogle Scholar
  53. 53.
    Okazaki H, Ito M, Sudo T, et al. IL-7 promotes thymocyte proliferation and maintains immunocompetent thymocytes bearing αß or T-cell receptors in vitro: synergism with IL-2. J Immunol 1989; 143: 2917–22.PubMedGoogle Scholar
  54. 54.
    Malkovsky M, Lovelan B, North M, et al. Recombinant interleukin-2 directly augments the cytotoxicity of human monocytes. Nature 1987; 325: 262–5.PubMedCrossRefGoogle Scholar
  55. 55.
    Tentori L, Longo DL, Zuniga-Pflucker JC, et al. Essential role of the interleukin-2-receptor pathway in thymocyte maturation in vivo. J Exp Med 1988; 168: 1741–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Leist TP, Kohler M, Eppler M, Zinkernagel RM. Effects of treatment with IL-2 receptor specific monoclonal antibody in mice: inhibition of cytotoxic T cell responses but not by T helper. J Immunol 1989; 143: 628–32.PubMedGoogle Scholar
  57. 57.
    Parmiani G, Anichini A, Fossati G. Cellular imune response against autologous human malignant melanoma: are in vistro studies providing a framework for a more effective immunotherapy? J Natl Cancer Inst 1990; 82: 361–70.PubMedCrossRefGoogle Scholar
  58. 58.
    Smyth MJ, Ortaldo JR, Bere W, et al. IL-2 and IL-6 synergize to augment the performing protein gene expression and cytotoxic potential of human peripheral blood T cells. J Immunol 1990: 145: 1159–66.PubMedGoogle Scholar
  59. 59.
    Chen W-F, Zlotnik A. IL-10: a novel cytotoxic T cell differentiation factor. J Immunol 1991; 147: 528–34.PubMedGoogle Scholar
  60. 60.
    Roder J. Killing comes naturally. Curr Biol 1991; 1: 242–4.PubMedCrossRefGoogle Scholar
  61. 61.
    Xiao J, Brahmi Z. Target cell-directed inactivation and IL-2 dependent reactivation of LAK cells. Cell Immunol 1989; 122: 295–306.PubMedCrossRefGoogle Scholar
  62. 62.
    Sone S, Utsugi T, Nii A, Ogura T. Differential effects of recombinant interferons α, ß and on induction of human lymphokine (IL-2)-activated killer activity. J Natl Cancer Inst 1988; 80: 425–31.PubMedCrossRefGoogle Scholar
  63. 63.
    Grimm EA, Mazumder A, Zhang HZ, et al. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin-2-activated autologous human peripheral blood lymphocyte. J Exp Med 1982; 155: 1823–41.PubMedCrossRefGoogle Scholar
  64. 64.
    Phillips JH, Lanier LL. Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med 1986; 164: 814–25.PubMedCrossRefGoogle Scholar
  65. 65.
    Lotze M, Custer MC, Sharrow SO, et al. In vivo administration of purified human interleukin-2 to patients with cancer: development of interleukin-2 receptor following interleukin-2 administration. Cancer Res. 1987; 47: 2188–95.PubMedGoogle Scholar
  66. 66.
    Gambacorti-Passerini C, Rivoltini L, Radrizzani M, et al. Differences between in vivo and in vitro activation of cancer patient lymphocytes by recombinant interleukin-2: possible role for lymphokine-activated killer cell infusion in the in vivo-induced activation. Cancer Res 1989; 49: 5230–4.PubMedGoogle Scholar
  67. 67.
    Grimm EA, Crump WL III, Durett A, et al. TGF-β inhibits the in vitro induction of lymphokine-activated killing activity. Cancer Immunol Immunother 1988; 27; 27: 53–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Farrar WJ, Johnson HM, Farrar JJ, Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin-2. J Immunol 1981; 126: 1120–5.PubMedGoogle Scholar
  69. 69.
    Dunn DE, Jin J, Lancki DW, Fitch FW. An alternate pathway of induction of lymphokine production by T lymphocyte clones. J Immunol 1989; 142: 3847–56.PubMedGoogle Scholar
  70. 70.
    Enokihara H, Furusawa S, Nakakubo H, et al. T cell from eosinophilic patients produce interleukin-2 with interleukin-5 stimulation. Blood 1989; 73: 1809–13.PubMedGoogle Scholar
  71. 71.
    Steen PD, McGregor JR, Lehman CM, Samlowski WE. Changes in homing receptor expression on murine lymphokine activated killer cells during IL-2 exposure. J Immunol 1989; 143: 4324–30.PubMedGoogle Scholar
  72. 72.
    Mazzocchi A, Rodolfo M, Parmiani G, Anichini A. An autologous T cell clone overcomes intra-melanoma heterogeneity for susceptibility to cell-mediated lysis by using multiple lytic mechanisms: in vitro and in vivo analysis. Melanoma Res 1991; 1: 169–76.PubMedGoogle Scholar
  73. 73.
    Gemlo BT, Palladino MA, Jaffe HS, et al. Circulating cytokines in patients with metastatic cancer treated with recombinant interleukin-2 and lymphokine-activated killer cells. Cancer Res 1988; 48: 5864–7.PubMedGoogle Scholar
  74. 74.
    Blay J-Y, Favrot MC, Negrier S, et al. Correlation between clinical response to interleukin-2 therapy and sustained production of tumor necrosis factor. Cancer Res 1990; 50: 2371–4.PubMedGoogle Scholar
  75. 75.
    Kornfeld H, Berman JS, Beer DJ, Center DM. Induction of human T lymphocyte motility by interleukin-2. J Immunol 1985; 134: 3887–90.PubMedGoogle Scholar
  76. 76.
    Ratner S, Heppner GH. Motility and tumoricidal activity of interleukin-2-stimulated lymphocytes. Cancer Res 1988; 48: 3374–80.PubMedGoogle Scholar
  77. 77.
    Ratner S. Lymphocytes stimulated with recombinant human interleukin-2: relationship between motility into protein matrix and in vivo localization in normal and neoplastic tissues of mice. J Natl Cancer Inst 1990; 82: 612–16.PubMedCrossRefGoogle Scholar
  78. 78.
    Whitehead RP, Ward D, Hemingway L, et al. Subcutaneous recombinant interleukin-2 in a dose escalating regimen in patients with metastatic renal cell adenocarcinoma. Cancer Res 1990; 50: 6708–15.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1993

Authors and Affiliations

  • Giorgio Parmiani
  • Carlo Gambacorti-Passerini

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