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Erschienen in:

01.11.2011 | Opinion Paper

Dual biological effects of the cytokines interleukin-10 and interferon-γ

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2011

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Abstract

It is generally thought that each cytokine exerts either immune stimulatory (inflammatory) or immune inhibitory (antiinflammatory or regulatory) biological activities. However, multiple cytokines can enact both inhibitory and stimulatory effects on the immune system. Two of these cytokines are interleukin (IL)-10 and interferon-gamma (IFNγ). IL-10 has demonstrated antitumor immunity even though it has been known for years as an immunoregulatory protein. Generally perceived as an immune stimulatory cytokine, IFNγ can also induce inhibitory molecule expression including B7-H1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), and arginase on multiple cell populations (dendritic cells, tumor cells, and vascular endothelial cells). In this review, we will summarize current knowledge of the dual roles of both of these cytokines and stress the previously underappreciated stimulatory role of IL-10 and inhibitory role of IFNγ in the context of malignancy. Our progressive understanding of the dual effects of these cytokines is important for dissecting cytokine-associated pathology and provides new avenues for developing effective immune therapy against human diseases, including cancer.

Fiorentino DF, Bond MW, Mosmann TR (1989) Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170(6):2081–2095PubMedCrossRef

O’Garra A, Stapleton G, Dhar V, Pearce M, Schumacher J, Rugo H, Barbis D, Stall A, Cupp J, Moore K et al (1990) Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol 2(9):821–832PubMedCrossRef

Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M (2005) Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol 23:749–786PubMedCrossRef

Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ (2007) Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 8(10):1095–1104PubMedCrossRef

Wei S, Kryczek I, Zou L, Daniel B, Cheng P, Mottram P, Curiel T, Lange A, Zou W (2005) Plasmacytoid dendritic cells induce CD8 + regulatory T cells in human ovarian carcinoma. Cancer Res 65(12):5020–5026PubMedCrossRef

Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 190(7):995–1004PubMedCrossRef

McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ (2007) TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8(12):1390–1397PubMedCrossRef

Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH (2000) Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192(9):1213–1222PubMedCrossRef

Khoo UY, Proctor IE, Macpherson AJ (1997) CD4 + T cell down-regulation in human intestinal mucosa: evidence for intestinal tolerance to luminal bacterial antigens. J Immunol 158(8):3626–3634PubMed

10.

Couper KN, Blount DG, Riley EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180(9):5771–5777PubMed

11.

Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765PubMedCrossRef

12.

Mosser DM, Zhang X (2008) Interleukin-10: new perspectives on an old cytokine. Immunol Rev 226:205–218PubMedCrossRef

13.

de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE (1991) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174(4):915–924PubMedCrossRef

14.

Ding L, Linsley PS, Huang LY, Germain RN, Shevach EM (1993) IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J Immunol 151(3):1224–1234PubMed

15.

Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562–567PubMedCrossRef

16.

Schandene L, Alonso-Vega C, Willems F, Gerard C, Delvaux A, Velu T, Devos R, de Boer M, Goldman M (1994) B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol 152(9):4368–4374PubMed

17.

Joss A, Akdis M, Faith A, Blaser K, Akdis CA (2000) IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 30(6):1683–1690PubMedCrossRef

18.

Demangel C, Bertolino P, Britton WJ (2002) Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production. Eur J Immunol 32(4):994–1002PubMedCrossRef

19.

Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4):295–307PubMedCrossRef

20.

Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, Kronenberg M (2009) Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 10(11):1178–1184PubMedCrossRef

21.

Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263–274PubMedCrossRef

22.

Davidson NJ, Leach MW, Fort MM, Thompson-Snipes L, Kuhn R, Muller W, Berg DJ, Rennick DM (1996) T helper cell 1-type CD4 + T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med 184(1):241–251PubMedCrossRef

23.

Zhou P, Streutker C, Borojevic R, Wang Y, Croitoru K (2004) IL-10 modulates intestinal damage and epithelial cell apoptosis in T cell-mediated enteropathy. Am J Physiol Gastrointest Liver Physiol 287(3):G599–G604PubMedCrossRef

24.

Jarry A, Bossard C, Bou-Hanna C, Masson D, Espaze E, Denis MG, Laboisse CL (2008) Mucosal IL-10 and TGF-beta play crucial roles in preventing LPS-driven, IFN-gamma-mediated epithelial damage in human colon explants. J Clin Invest 118(3):1132–1142PubMed

25.

Hagenbaugh A, Sharma S, Dubinett SM, Wei SH, Aranda R, Cheroutre H, Fowell DJ, Binder S, Tsao B, Locksley RM, Moore KW, Kronenberg M (1997) Altered immune responses in interleukin 10 transgenic mice. J Exp Med 185(12):2101–2110PubMedCrossRef

26.

Peters N, Sacks D (2006) Immune privilege in sites of chronic infection: Leishmania and regulatory T cells. Immunol Rev 213:159–179PubMedCrossRef

27.

van der Sluijs KF, van Elden LJ, Nijhuis M, Schuurman R, Pater JM, Florquin S, Goldman M, Jansen HM, Lutter R, van der Poll T (2004) IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J Immunol 172(12):7603–7609PubMed

28.

Jimenez Mdel P, Walls L, Fierer J (2006) High levels of interleukin-10 impair resistance to pulmonary coccidioidomycosis in mice in part through control of nitric oxide synthase 2 expression. Infect Immun 74(6):3387–3395PubMedCrossRef

29.

Fierer J, Walls L, Eckmann L, Yamamoto T, Kirkland TN (1998) Importance of interleukin-10 in genetic susceptibility of mice to Coccidioides immitis. Infect Immun 66(9):4397–4402PubMed

30.

Kelly JP, Bancroft GJ (1996) Administration of interleukin-10 abolishes innate resistance to Listeria monocytogenes. Eur J Immunol 26(2):356–364PubMedCrossRef

31.

Kim BG, Joo HG, Chung IS, Chung HY, Woo HJ, Yun YS (2000) Inhibition of interleukin-10 (IL-10) production from MOPC 315 tumor cells by IL-10 antisense oligodeoxynucleotides enhances cell-mediated immune responses. Cancer Immunol Immunother 49(8):433–440PubMedCrossRef

32.

Matar P, Rozados VR, Gervasoni SI, Scharovsky OG (2001) Down regulation of T-cell-derived IL-10 production by low-dose cyclophosphamide treatment in tumor-bearing rats restores in vitro normal lymphoproliferative response. Int Immunopharmacol 1(2):307–319PubMedCrossRef

33.

Vicari AP, Chiodoni C, Vaure C, Ait-Yahia S, Dercamp C, Matsos F, Reynard O, Taverne C, Merle P, Colombo MP, O’Garra A, Trinchieri G, Caux C (2002) Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody. J Exp Med 196(4):541–549PubMedCrossRef

34.

Enk AH, Jonuleit H, Saloga J, Knop J (1997) Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int J Cancer 73(3):309–316PubMedCrossRef

35.

Loercher AE, Nash MA, Kavanagh JJ, Platsoucas CD, Freedman RS (1999) Identification of an IL-10-producing HLA-DR-negative monocyte subset in the malignant ascites of patients with ovarian carcinoma that inhibits cytokine protein expression and proliferation of autologous T cells. J Immunol 163(11):6251–6260PubMed

36.

De Santo C, Arscott R, Booth S, Karydis I, Jones M, Asher R, Salio M, Middleton M, Cerundolo V (2010) Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat Immunol 11(11):1039–1046PubMedCrossRef

37.

Seo N, Hayakawa S, Tokura Y (2002) Mechanisms of immune privilege for tumor cells by regulatory cytokines produced by innate and acquired immune cells. Semin Cancer Biol 12(4):291–300PubMedCrossRef

38.

Kurte M, Lopez M, Aguirre A, Escobar A, Aguillon JC, Charo J, Larsen CG, Kiessling R, Salazar-Onfray F (2004) A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and transporter associated with antigen processing 1/2 in human melanoma cells. J Immunol 173(3):1731–1737PubMed

39.

Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nickoloff BJ, Uyemura K (1995) IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. J Immunol 155(4):2240–2247PubMed

40.

Steinbrink K, Jonuleit H, Muller G, Schuler G, Knop J, Enk AH (1999) Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 93(5):1634–1642PubMed

41.

Urosevic M, Dummer R (2003) HLA-G and IL-10 expression in human cancer–different stories with the same message. Semin Cancer Biol 13(5):337–342PubMedCrossRef

42.

Jovasevic VM, Gorelik L, Bluestone JA, Mokyr MB (2004) Importance of IL-10 for CTLA-4-mediated inhibition of tumor-eradicating immunity. J Immunol 172(3):1449–1454PubMed

43.

Huang M, Stolina M, Sharma S, Mao JT, Zhu L, Miller PW, Wollman J, Herschman H, Dubinett SM (1998) Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res 58(6):1208–1216PubMed

44.

Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, Zhu L, Kronenberg M, Miller PW, Portanova J, Lee JC, Dubinett SM (2000) Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol 164(1):361–370PubMed

45.

Sharma S, Stolina M, Yang SC, Baratelli F, Lin JF, Atianzar K, Luo J, Zhu L, Lin Y, Huang M, Dohadwala M, Batra RK, Dubinett SM (2003) Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin Cancer Res 9(3):961–968PubMed

46.

Go NF, Castle BE, Barrett R, Kastelein R, Dang W, Mosmann TR, Moore KW, Howard M (1990) Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med 172(6):1625–1631PubMedCrossRef

47.

Rousset F, Garcia E, Defrance T, Peronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J (1992) Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 89(5):1890–1893PubMedCrossRef

48.

Llorente L, Zou W, Levy Y, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J, Morel-Fourrier B, Brouet JC, Alarcon-Segovia D, Galanaud P, Emilie D (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181(3):839–844PubMedCrossRef

49.

Levy Y, Brouet JC (1994) Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest 93(1):424–428PubMedCrossRef

50.

Liu YJ, Mason DY, Johnson GD, Abbot S, Gregory CD, Hardie DL, Gordon J, MacLennan IC (1991) Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol 21(8):1905–1910PubMedCrossRef

51.

MacNeil IA, Suda T, Moore KW, Mosmann TR, Zlotnik A (1990) IL-10, a novel growth cofactor for mature and immature T cells. J Immunol 145(12):4167–4173PubMed

52.

Chen WF, Zlotnik A (1991) IL-10: a novel cytotoxic T cell differentiation factor. J Immunol 147(2):528–534PubMed

53.

Mocellin S, Marincola FM, Young HA (2005) Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 78(5):1043–1051PubMedCrossRef

54.

Suzuki T, Tahara H, Narula S, Moore KW, Robbins PD, Lotze MT (1995) Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors. J Exp Med 182(2):477–486PubMedCrossRef

55.

Zheng LM, Ojcius DM, Garaud F, Roth C, Maxwell E, Li Z, Rong H, Chen J, Wang XY, Catino JJ, King I (1996) Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism. J Exp Med 184(2):579–584PubMedCrossRef

56.

Kundu N, Fulton AM (1997) Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis. Cell Immunol 180(1):55–61PubMedCrossRef

57.

Karre K (1993) Natural killer cells and the MHC class I pathway of peptide presentation. Semin Immunol 5(2):127–145PubMedCrossRef

58.

Fujii S, Shimizu K, Shimizu T, Lotze MT (2001) Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood 98(7):2143–2151PubMedCrossRef

59.

Tanikawa T, Wilke CM, Kryczek I, Chen GY, Kao JY, Zou W (2011) Ablation of interleukin (IL)-10 promotes tumor development, growth and metastasis (in press)

60.

Zhou Z, Peng X, Insolera R, Fink DJ, Mata M (2009) Interleukin-10 provides direct trophic support to neurons. J Neurochem 110(5):1617–1627PubMedCrossRef

61.

Park HJ, Lee SJ, Kim SH, Han J, Bae J, Kim SJ, Park CG, Chun T (2011) IL-10 inhibits the starvation induced autophagy in macrophages via class I phosphatidylinositol 3-kinase (PI3 K) pathway. Mol Immunol 48(4):720–727PubMedCrossRef

62.

Dace DS, Khan AA, Kelly J, Apte RS (2008) Interleukin-10 promotes pathological angiogenesis by regulating macrophage response to hypoxia during development. PLoS One 3(10):e3381PubMedCrossRef

63.

Isaacs A, Lindenmann J (1957) Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147(927):258–267PubMedCrossRef

64.

Isaacs A, Lindenmann J, Valentine RC (1957) Virus interference. II. Some properties of interferon. Proc R Soc Lond B Biol Sci 147(927):268–273PubMedCrossRef

65.

Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K (1998) IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 161(7):3400–3407PubMed

66.

Munder M, Mallo M, Eichmann K, Modolell M (1998) Murine macrophages secrete interferon gamma upon combined stimulation with interleukin (IL)-12 and IL-18: a novel pathway of autocrine macrophage activation. J Exp Med 187(12):2103–2108PubMedCrossRef

67.

Tominaga K, Yoshimoto T, Torigoe K, Kurimoto M, Matsui K, Hada T, Okamura H, Nakanishi K (2000) IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int Immunol 12(2):151–160PubMedCrossRef

68.

Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378(6552):88–91PubMedCrossRef

69.

Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, Sana T, Hartley SB, Menon S, Kastelein R, Bazan F, O’Garra A (1997) IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB. Immunity 7(4):571–581PubMedCrossRef

70.

Yoshimoto T, Okamura H, Tagawa YI, Iwakura Y, Nakanishi K (1997) Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc Natl Acad Sci USA 94(8):3948–3953PubMedCrossRef

71.

Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6(11):836–848PubMedCrossRef

72.

Blankenstein T, Qin Z (2003) Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance. Adv Cancer Res 90:179–207PubMedCrossRef

73.

Wallach D, Fellous M, Revel M (1982) Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature 299(5886):833–836PubMedCrossRef

74.

Johnson DR, Pober JS (1990) Tumor necrosis factor and immune interferon synergistically increase transcription of HLA class I heavy- and light-chain genes in vascular endothelium. Proc Natl Acad Sci USA 87(13):5183–5187PubMedCrossRef

75.

Billiau A, Heremans H, Vandekerckhove F, Dijkmans R, Sobis H, Meulepas E, Carton H (1988) Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J Immunol 140(5):1506–1510PubMed

76.

Mach B, Steimle V, Martinez-Soria E, Reith W (1996) Regulation of MHC class II genes: lessons from a disease. Annu Rev Immunol 14:301–331PubMedCrossRef

77.

Groettrup M, Khan S, Schwarz K, Schmidtke G (2001) Interferon-gamma inducible exchanges of 20S proteasome active site subunits: why? Biochimie 83(3–4):367–372PubMedCrossRef

78.

Nathan CF, Murray HW, Wiebe ME, Rubin BY (1983) Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158(3):670–689PubMedCrossRef

79.

Flaishon L, Hershkoviz R, Lantner F, Lider O, Alon R, Levo Y, Flavell RA, Shachar I (2000) Autocrine secretion of interferon gamma negatively regulates homing of immature B cells. J Exp Med 192(9):1381–1388PubMedCrossRef

80.

Finkelman FD, Katona IM, Mosmann TR, Coffman RL (1988) IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 140(4):1022–1027PubMed

81.

Balkwill F, Taylor-Papadimitriou J (1978) Interferon affects both G1 and S + G2 in cells stimulated from quiescence to growth. Nature 274(5673):798–800PubMedCrossRef

82.

Xaus J, Cardo M, Valledor AF, Soler C, Lloberas J, Celada A (1999) Interferon gamma induces the expression of p21waf-1 and arrests macrophage cell cycle, preventing induction of apoptosis. Immunity 11(1):103–113PubMedCrossRef

83.

Shiohara M, Koike K, Nakahata T (1993) Synergism of interferon-gamma and stem cell factor on the development of murine hematopoietic progenitors in serum-free culture. Blood 81(6):1435–1441PubMed

84.

Gajewski TF, Fitch FW (1988) Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol 140(12):4245–4252PubMed

85.

Yoshida A, Koide Y, Uchijima M, Yoshida TO (1994) IFN-gamma induces IL-12 mRNA expression by a murine macrophage cell line, J774. Biochem Biophys Res Commun 198(3):857–861PubMedCrossRef

86.

Kryczek I, Wei S, Gong W, Shu X, Szeliga W, Vatan L, Chen L, Wang G, Zou W (2008) Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol 181(9):5842–5846PubMed

87.

Zou W, Restifo NP (2010) T(H)17 cells in tumour immunity and immunotherapy. Nat Rev Immunol 10(4):248–256PubMedCrossRef

88.

Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, Vatan L, Szeliga W, Wang Y, Liu Y, Welling TH, Elder JT, Zou W (2008) Induction of IL-17 + T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181(7):4733–4741PubMed

89.

Feng T, Qin H, Wang L, Benveniste EN, Elson CO, Cong Y (2011) Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol

90.

Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, Vilcek J, Zinkernagel RM, Aguet M (1993) Immune response in mice that lack the interferon-gamma receptor. Science 259(5102):1742–1745PubMedCrossRef

91.

Cantin E, Tanamachi B, Openshaw H (1999) Role for gamma interferon in control of herpes simplex virus type 1 reactivation. J Virol 73(4):3418–3423PubMed

92.

Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM, Aguet M (1994) Functional role of type I and type II interferons in antiviral defense. Science 264(5167):1918–1921PubMedCrossRef

93.

Levin M, Newport MJ, D’Souza S, Kalabalikis P, Brown IN, Lenicker HM, Agius PV, Davies EG, Thrasher A, Klein N et al (1995) Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene? Lancet 345(8942):79–83PubMedCrossRef

94.

Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, Levin M (1996) A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 335(26):1941–1949PubMedCrossRef

95.

Jouanguy E, Lamhamedi-Cherradi S, Lammas D, Dorman SE, Fondaneche MC, Dupuis S, Doffinger R, Altare F, Girdlestone J, Emile JF, Ducoulombier H, Edgar D, Clarke J, Oxelius VA, Brai M, Novelli V, Heyne K, Fischer A, Holland SM, Kumararatne DS, Schreiber RD, Casanova JL (1999) A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet 21(4):370–378PubMedCrossRef

96.

Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA (2010) Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature 465(7299):793–797PubMedCrossRef

97.

Ikeda H, Old LJ, Schreiber RD (2002) The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev 13(2):95–109PubMedCrossRef

98.

Dighe AS, Richards E, Old LJ, Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1(6):447–456PubMedCrossRef

99.

Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95(13):7556–7561PubMedCrossRef

100.

Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97(1):192–197PubMedCrossRef

101.

Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410(6832):1107–1111PubMedCrossRef

102.

Qin Z, Blankenstein T (2004) A cancer immunosurveillance controversy. Nat Immunol 5 (1):3-4 (author reply 4–5)

103.

Schreiber TH, Podack ER (2009) A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas. Br J Cancer 101(3):381–386PubMedCrossRef

104.

Schreiber RD, Celada A, Buchmeier N (1986) The role of interferon-gamma in the induction of activated macrophages. Ann Inst Pasteur Immunol 137C(2):203–206PubMedCrossRef

105.

Dighe AS, Campbell D, Hsieh CS, Clarke S, Greaves DR, Gordon S, Murphy KM, Schreiber RD (1995) Tissue-specific targeting of cytokine unresponsiveness in transgenic mice. Immunity 3(5):657–666PubMedCrossRef

106.

Murphy TL, Cleveland MG, Kulesza P, Magram J, Murphy KM (1995) Regulation of interleukin 12 p40 expression through an NF-kappa B half-site. Mol Cell Biol 15(10):5258–5267PubMed

107.

Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A (1999) Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163(9):4647–4650PubMed

108.

Eberl G, MacDonald HR (2000) Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur J Immunol 30(4):985–992PubMedCrossRef

109.

Badovinac VP, Tvinnereim AR, Harty JT (2000) Regulation of antigen-specific CD8 + T cell homeostasis by perforin and interferon-gamma. Science 290(5495):1354–1358PubMedCrossRef

110.

Whitmire JK, Tan JT, Whitton JL (2005) Interferon-gamma acts directly on CD8 + T cells to increase their abundance during virus infection. J Exp Med 201(7):1053–1059PubMedCrossRef

111.

Bradley LM, Dalton DK, Croft M (1996) A direct role for IFN-gamma in regulation of Th1 cell development. J Immunol 157(4):1350–1358PubMed

112.

Scott P (1991) IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. J Immunol 147(9):3149–3155PubMed

113.

Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W (2009) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149PubMedCrossRef

114.

Fallarino F, Gajewski TF (1999) Cutting edge: differentiation of antitumor CTL in vivo requires host expression of Stat1. J Immunol 163(8):4109–4113PubMed

115.

Kacha AK, Fallarino F, Markiewicz MA, Gajewski TF (2000) Cutting edge: spontaneous rejection of poorly immunogenic P1. HTR tumors by Stat6-deficient mice. J Immunol 165(11):6024–6028PubMed

116.

Cao X, Leonard K, Collins LI, Cai SF, Mayer JC, Payton JE, Walter MJ, Piwnica-Worms D, Schreiber RD, Ley TJ (2009) Interleukin 12 stimulates IFN-gamma-mediated inhibition of tumor-induced regulatory T-cell proliferation and enhances tumor clearance. Cancer Res 69(22):8700–8709PubMedCrossRef

117.

Luster AD, Ravetch JV (1987) Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 166(4):1084–1097PubMedCrossRef

118.

Luster AD, Leder P (1993) IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo. J Exp Med 178(3):1057–1065PubMedCrossRef

119.

Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8(6):467–477PubMedCrossRef

120.

Wu K, Kryczek I, Chen L, Zou W, Welling TH (2009) Kupffer cell suppression of CD8 + T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions. Cancer Res 69(20):8067–8075PubMedCrossRef

121.

Wiendl H, Mitsdoerffer M, Schneider D, Chen L, Lochmuller H, Melms A, Weller M (2003) Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies. FASEB J 17(13):1892–1894PubMed

122.

Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800PubMed

123.

Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, Saudemont A, Quesnel B (2007) Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood 110(1):296–304PubMedCrossRef

124.

Kondo A, Yamashita T, Tamura H, Zhao W, Tsuji T, Shimizu M, Shinya E, Takahashi H, Tamada K, Chen L, Dan K, Ogata K (2010) Interferon-gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes. Blood 116(7):1124–1131PubMedCrossRef

125.

Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2, 3-dioxygenase. Science 297(5588):1867–1870PubMedCrossRef

126.

Carlin JM, Borden EC, Sondel PM, Byrne GI (1987) Biologic-response-modifier-induced indoleamine 2, 3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J Immunol 139(7):2414–2418PubMed

127.

Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5(4):263–274PubMedCrossRef

128.

Mellor AL, Munn DH (2008) Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol 8(1):74–80PubMedCrossRef

129.

Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC (2005) Inhibition of indoleamine 2, 3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 11(3):312–319PubMedCrossRef

130.

Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH (2007) Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J Clin Invest 117(9):2570–2582PubMedCrossRef

131.

Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 4(12):1206–1212PubMedCrossRef

132.

Muller AJ, Sharma MD, Chandler PR, Duhadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL (2008) Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2, 3 dioxygenase. Proc Natl Acad Sci USA 105(44):17073–17078PubMedCrossRef

133.

Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC (2003) l-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol 171(3):1232–1239PubMed

134.

Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, Antonia S, Ochoa JB, Ochoa AC (2004) Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64(16):5839–5849PubMedCrossRef

135.

Saio M, Radoja S, Marino M, Frey AB (2001) Tumor-infiltrating macrophages induce apoptosis in activated CD8(+) T cells by a mechanism requiring cell contact and mediated by both the cell-associated form of TNF and nitric oxide. J Immunol 167(10):5583–5593PubMed

136.

Kusmartsev SA, Li Y, Chen SH (2000) Gr-1 + myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J Immunol 165(2):779–785PubMed

137.

Liscovsky MV, Ranocchia RP, Gorlino CV, Alignani DO, Moron G, Maletto BA, Pistoresi-Palencia MC (2009) Interferon-gamma priming is involved in the activation of arginase by oligodeoxinucleotides containing CpG motifs in murine macrophages. Immunology 128(1 Suppl):e159–e169PubMedCrossRef

138.

Mazzoni A, Bronte V, Visintin A, Spitzer JH, Apolloni E, Serafini P, Zanovello P, Segal DM (2002) Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol 168(2):689–695PubMed

139.

Modolell M, Corraliza IM, Link F, Soler G, Eichmann K (1995) Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines. Eur J Immunol 25(4):1101–1104PubMedCrossRef

140.

Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, Pearce EJ, Wynn TA (2001) Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of l-arginine metabolism. J Immunol 167(11):6533–6544PubMed

141.

Norian LA, Rodriguez PC, O’Mara LA, Zabaleta J, Ochoa AC, Cella M, Allen PM (2009) Tumor-infiltrating regulatory dendritic cells inhibit CD8 + T cell function via l-arginine metabolism. Cancer Res 69(7):3086–3094PubMedCrossRef

142.

Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A, Mier J, Ochoa AC (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65(8):3044–3048PubMed

143.

Ochoa AC, Zea AH, Hernandez C, Rodriguez PC (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13(2 Pt 2):721s–726sPubMedCrossRef

144.

Rodriguez PC, Ochoa AC (2008) Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev 222:180–191PubMedCrossRef

145.

Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553–1560PubMedCrossRef

146.

Highfill SL, Rodriguez PC, Zhou Q, Goetz CA, Koehn BH, Veenstra R, Taylor PA, Panoskaltsis-Mortari A, Serody JS, Munn DH, Tolar J, Ochoa AC, Blazar BR (2010) Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood 116(25):5738–5747PubMedCrossRef

147.

Ilangumaran S, Rottapel R (2003) Regulation of cytokine receptor signaling by SOCS1. Immunol Rev 192:196–211PubMedCrossRef

148.

Starr R, Fuchsberger M, Lau LS, Uldrich AP, Goradia A, Willson TA, Verhagen AM, Alexander WS, Smyth MJ (2009) SOCS-1 binding to tyrosine 441 of IFN-gamma receptor subunit 1 contributes to the attenuation of IFN-gamma signaling in vivo. J Immunol 183(7):4537–4544PubMedCrossRef

149.

Taniguchi K, Petersson M, Hoglund P, Kiessling R, Klein G, Karre K (1987) Interferon gamma induces lung colonization by intravenously inoculated B16 melanoma cells in parallel with enhanced expression of class I major histocompatibility complex antigens. Proc Natl Acad Sci USA 84(10):3405–3409PubMedCrossRef

150.

Cho HI, Lee YR, Celis E (2010) Interferon gamma limits the effectiveness of melanoma peptide vaccines. Blood

151.

Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL, Monsarrat B, Van Velthoven R, Cerottini JC, Boon T, Gairin JE, Van den Eynde BJ (2000) Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 12(1):107–117PubMedCrossRef

152.

Gobin SJ, van den Elsen PJ (2000) Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G. Hum Immunol 61(11):1102–1107PubMedCrossRef

153.

Zaidi MR, Davis S, Noonan FP, Graff-Cherry C, Hawley TS, Walker RL, Feigenbaum L, Fuchs E, Lyakh L, Young HA, Hornyak TJ, Arnheiter H, Trinchieri G, Meltzer PS, De Fabo EC, Merlino G (2011) Interferon-gamma links ultraviolet radiation to melanomagenesis in mice. Nature 469(7331):548–553PubMedCrossRef

154.

Berner V, Liu H, Zhou Q, Alderson KL, Sun K, Weiss JM, Back TC, Longo DL, Blazar BR, Wiltrout RH, Welniak LA, Redelman D, Murphy WJ (2007) IFN-gamma mediates CD4 + T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy. Nat Med 13(3):354–360PubMedCrossRef

155.

Garbe C, Krasagakis K, Zouboulis CC, Schroder K, Kruger S, Stadler R, Orfanos CE (1990) Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype. J Invest Dermatol 95(6 Suppl):231S–237SPubMedCrossRef

156.

Creagan ET, Ahmann DL, Long HJ, Frytak S, Sherwin SA, Chang MN (1987) Phase II study of recombinant interferon-gamma in patients with disseminated malignant melanoma. Cancer Treat Rep 71(9):843–844PubMed

157.

Ernstoff MS, Trautman T, Davis CA, Reich SD, Witman P, Balser J, Rudnick S, Kirkwood JM (1987) A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma. J Clin Oncol 5(11):1804–1810PubMed

158.

Kopp WC, Smith JW II, Ewel CH, Alvord WG, Main C, Guyre PM, Steis RG, Longo DL, Urba WJ (1993) Immunomodulatory effects of interferon-gamma in patients with metastatic malignant melanoma. J Immunother Emphas Tumor Immunol 13(3):181–190

159.

Kowalzick L, Weyer U, Lange P, Breitbart EW (1990) Systemic therapy of advanced metastatic malignant melanoma with a combination of fibroblast interferon-beta and recombinant interferon-gamma. Dermatologica 181(4):298–303PubMedCrossRef

160.

Meyskens FL Jr, Kopecky K, Samson M, Hersh E, Macdonald J, Jaffe H, Crowley J, Coltman C (1990) Recombinant human interferon gamma: adverse effects in high-risk stage I and II cutaneous malignant melanoma. J Natl Cancer Inst 82(12):1071PubMed

161.

Meyskens FL Jr, Kopecky KJ, Taylor CW, Noyes RD, Tuthill RJ, Hersh EM, Feun LG, Doroshow JH, Flaherty LE, Sondak VK (1995) Randomized trial of adjuvant human interferon gamma versus observation in high-risk cutaneous melanoma: a southwest oncology group study. J Natl Cancer Inst 87(22):1710–1713PubMedCrossRef

162.

Coughlin CM, Salhany KE, Gee MS, LaTemple DC, Kotenko S, Ma X, Gri G, Wysocka M, Kim JE, Liu L, Liao F, Farber JM, Pestka S, Trinchieri G, Lee WM (1998) Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9(1):25–34PubMedCrossRef

163.

Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y, Fu XY (1996) Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1. Science 272(5262):719–722PubMedCrossRef

164.

Bromberg JF, Horvath CM, Wen Z, Schreiber RD, Darnell JE Jr (1996) Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc Natl Acad Sci USA 93(15):7673–7678PubMedCrossRef

165.

Sgadari C, Angiolillo AL, Cherney BW, Pike SE, Farber JM, Koniaris LG, Vanguri P, Burd PR, Sheikh N, Gupta G, Teruya-Feldstein J, Tosato G (1996) Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. Proc Natl Acad Sci USA 93(24):13791–13796PubMedCrossRef

166.

Arenberg DA, Kunkel SL, Polverini PJ, Morris SB, Burdick MD, Glass MC, Taub DT, Iannettoni MD, Whyte RI, Strieter RM (1996) Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J Exp Med 184(3):981–992PubMedCrossRef

167.

Sgadari C, Farber JM, Angiolillo AL, Liao F, Teruya-Feldstein J, Burd PR, Yao L, Gupta G, Kanegane C, Tosato G (1997) Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo. Blood 89(8):2635–2643PubMed

168.

Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE, Hunter CA, Fox JC, Trinchieri G, Lee WM (1998) Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest 101(6):1441–1452PubMedCrossRef

169.

Briesemeister D, Sommermeyer D, Loddenkemper C, Loew R, Uckert W, Blankenstein T, Kammertoens T (2011) Tumor rejection by local interferon gamma induction in established tumors is associated with blood vessel destruction and necrosis. Int J Cancer 128(2):371–378PubMedCrossRef

170.

Groux H, Bigler M, de Vries JE, Roncarolo MG (1998) Inhibitory and stimulatory effects of IL-10 on human CD8 + T cells. J Immunol 160(7):3188–3193PubMed

Titel: Dual biological effects of the cytokines interleukin-10 and interferon-γ
Publikationsdatum: 01.11.2011
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2011
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1104-5

Springer Medizin

Dual biological effects of the cytokines interleukin-10 and interferon-γ

Abstract

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Springer Medizin

Abstract

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