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  • 1
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    Kirman, I., Vainer, B. and Nielsen, O. H., Interleukin-15 and its role in chronic inflammatory diseases. Inflamm. Res. 1998. 47: 285289.
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    Perera, L. P., Interleukin 15: its role in inflammation and immunity. Arch. Immunol. Ther. Exp. (Warsz) 2000. 48: 457464.
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    Lodolce, J., Burkett, P., Koka, R., Boone, D., Chien, M., Chan, F., Madonia, M. et al., Interleukin-15 and the regulation of lymphoid homeostasis. Mol. Immunol. 2002. 39: 537544.
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    Carson, W. E., Giri, J. G., Lindemann, M. J., Linett, M. L., Ahdieh, M., Paxton, R., Anderson, D. et al., Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J. Exp. Med. 1994. 180: 13951403.
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    Giri, J. G., Ahdieh, M., Eisenman, J., Shanebeck, K., Grabstein, K., Kumaki, S., Namen, A. et al., Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J. 1994. 13: 28222830.
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    Grabstein, K. H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., Beers, C. et al., Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 1994. 264: 965968.
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    Cosman, D., Kumaki, S., Ahdieh, M., Eisenman, J., Grabstein, K. H., Paxton, R., DuBose, R. et al., Interleukin 15 and its receptor. Ciba Found. Symp. 1995. 195: 221229.
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    Giri, J. G., Kumaki, S., Ahdieh, M., Friend, D. J., Loomis, A., Shanebeck, K., DuBose, R. et al., Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor. EMBO J. 1995. 14: 36543663.
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    Anderson, D. M., Kumaki, S., Ahdieh, M., Bertles, J., Tometsko, M., Loomis, A., Giri, J. et al., Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. J. Biol. Chem. 1995. 270: 2986229869.
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    Agostini, C., Trentin, L., Sancetta, R., Facco, M., Tassinari, C., Cerutti, A., Bortolin, M. et al., Interleukin-15 triggers activation and growth of the CD8 T-cell pool in extravascular tissues of patients with acquired immunodeficiency syndrome. Blood 1997. 90: 11151123.
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    Li, X. C., Demirci, G., Ferrari-Lacraz, S., Groves, C., Coyle, A., Malek, T. R. and Strom, T. B., IL-15 and IL-2: a matter of life and death for T cells in vivo. Nat. Med. 2001. 7: 114118.
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    De Winter, H., Cheroutre, H. and Kronenberg, M., Mucosal immunity and inflammation. II. The yin and yang of T cells in intestinal inflammation: pathogenic and protective roles in a mouse colitis model. Am. J. Physiol. 1999. 276: 13171321.
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    Iqbal, N., Oliver, J. R., Wagner, F. H., Lazenby, A. S., Elson, C. O. and Weaver, C. T., T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis. J. Exp. Med. 2002. 195: 7184.
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    Watanabe, M., Hosoda, Y., Okamoto, S., Yamazaki, M., Inoue, N., Ueno, Y., Iwao, Y. et al., CD45RChighCD4+ intestinal mucosal lymphocytes infiltrating in the inflamed colonic mucosa of a novel rat colitis model induced by TNB immunization. Clin. Immunol. Immunopathol. 1998. 88: 4655.
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    Simpson, S. J., Shah, S., Comiskey, M., de Jong, Y. P., Wang, B., Mizoguchi, E., Bhan, A. K. et al., T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells. J. Exp. Med. 1998. 187: 12251234.
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    Elson, C. O., Beagley, K. W., Sharmanov, A. T., Fujihashi, K., Kiyono, H., Tennyson, G. S., Cong, Y. et al., Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J. Immunol. 1996. 157: 21742185.
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    Neurath, M. F., Fuss, I., Kelsall, B. L., Stuber, E. and Strober, W., Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exp. Med. 1995. 182: 12811290.
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    Powrie, F., Leach, M. W., Mauze, S., Menon, S., Caddle, L. B. and Coffman, R. L., Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1994. 1: 553562.
  • 20
    Bulfone-Paus, S., Durkop, H., Paus, R., Krause, H., Pohl, T. and Onu, A., Differential regulation of human T lymphoblast functions by IL-2 and IL- 15. Cytokine 1997. 9: 507513.
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    Lorenz, H. M., Hieronymus, T., Grunke, M., Manger, B. and Kalden, J. R., Differential role for IL-2 and IL-15 in the inhibition of apoptosis in short-term activated human lymphocytes. Scand. J. Immunol. 1997. 45: 660669.
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    Bulfone-Paus, S., Ungureanu, D., Pohl, T., Lindner, G., Paus, R., Ruckert, R., Krause, H. et al., Interleukin-15 protects from lethal apoptosis in vivo. Nat. Med. 1997. 3: 11241128.
  • 23
    Inagaki-Ohara, K., Nishimura, H., Mitani, A. and Yoshikai, Y., Interleukin-15 preferentially promotes the growth of intestinal intraepithelial lymphocytes bearing gamma delta T cell receptor in mice. Eur. J. Immunol. 1997. 27: 28852891.
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    Chu, C. L., Chen, S. S., Wu, T. S., Kuo, S. C. and Liao, N. S., Differential effects of IL-2 and IL-15 on the death and survival of activated TCR gamma delta+ intestinal intraepithelial lymphocytes. J. Immunol. 1999. 162: 18961903.
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    Naora, H. and Gougeon, M. L., Interleukin-15 is a potent survival factor in the prevention of spontaneous but not CD95-induced apoptosis in CD4 and CD8 T lymphocytes of HIV-infected individuals. Correlation with its ability to increase BCL-2 expression. Cell Death Differ. 1999. 6: 10021011.
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    Kanegane, H. and Tosato, G., Activation of naive and memory T cells by interleukin-15. Blood 1996. 88: 230235.
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    Lai, Y. G., Gelfanov, V., Gelfanova, V., Kulik, L., Chu, C. L., Jeng, S. W. and Liao, N. S., IL-15 promotes survival but not effector function differentiation of CD8+ TCRalphabeta+ intestinal intraepithelial lymphocytes. J. Immunol. 1999. 163: 58435850.
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    Niedbala, W., Wei, X. and Liew, F. Y., IL-15 induces type 1 and type 2 CD4+ and CD8+ T cells proliferation but is unable to drive cytokine production in the absence of TCR activation or IL-12 / IL-4 stimulation in vitro. Eur. J. Immunol. 2002. 32: 341347.
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    Thulesen, S., Nielsen, M., Petersen, T. R., Holst Nissen, M., Odum, N. and Ropke, C., Interleukin 15 is a growth factor for human thymocytes with preferential effect on CD8(+)cells. Cytokine 2000. 12: 751755.
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    Reinecker, H. C., MacDermott, R. P., Mirau, S., Dignass, A. and Podolsky, D. K., Intestinal epithelial cells both express and respond to interleukin 15. Gastroenterology 1996. 111: 17061713.
  • 31
    Sakai, T., Kusugami, K., Nishimura, H., Ando, T., Yamaguchi, T., Ohsuga, M., Ina, K. et al., Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease. Gastroenterology 1998. 114: 12371243.
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    Murray, A. M., Simm, B. and Beagley, K. W., Cytokine gene expression in murine fetal intestine: potential for extrathymic T cell development. Cytokine 1998. 10: 337345.
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    Liu, Z., Geboes, K., Colpaert, S., D'Haens, G. R., Rutgeerts, P. and Ceuppens, J. L., IL-15 is highly expressed in inflammatory bowel disease and regulates local T cell-dependent cytokine production. J. Immunol. 2000. 164: 36083615.
  • 34
    Hiroi, T., Yanagita, M., Ohta, N., Sakaue, G. and Kiyono, H., IL-15 and IL-15 receptor selectively regulate differentiation of common mucosal immune system-independent B-1 cells for IgA responses. J. Immunol. 2000. 165: 43294337.
  • 35
    McInnes, I. B. and Liew, F. Y., Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis. Immunol. Today 1998. 19: 7579.
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    McInnes, I. B., Leung, B. P., Sturrock, R. D., Field, M. and Liew, F. Y., Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat. Med. 1997. 3: 189195.
  • 37
    McInnes, I. B., al-Mughales, J., Field, M., Leung, B. P., Huang, F. P., Dixon, R., Sturrock, R. D. et al., The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. Nat. Med. 1996. 2: 175182.
  • 38
    Carson, D. A., Unconventional T-cell activation by IL-15 in rheumatoid arthritis. Nat. Med. 1997. 3: 148149.
  • 39
    Thurkow, E. W., van der Heijden, I. M., Breedveld, F. C., Smeets, T. J., Daha, M. R., Kluin, P. M., Meinders, A. E. et al., Increased expression of IL-15 in the synovium of patients with rheumatoid arthritis compared with patients with Yersinia-induced arthritis and osteoarthritis. J. Pathol. 1997. 181: 444450.
  • 40
    Shah, M. H., Hackshaw, K. V. and Caligiuri, M. A., A role for IL-15 in rheumatoid arthritis? Nat. Med. 1998. 4: 643.
  • 41
    Kirman, I. and Nielsen, O. H., Increased numbers of interleukin-15-expressing cells in active ulcerative colitis. Am. J. Gastroenterol. 1996. 91: 17891794.
  • 42
    Vainer, B., Nielsen, O. H., Hendel, J., Horn, T. and Kirman, I., Colonic expression and synthesis of interleukin 13 and interleukin 15 in inflammatory bowel disease. Cytokine 2000. 12: 15311536.
  • 43
    Pavlakis, M., Strehlau, J., Lipman, M., Shapiro, M., Maslinski, W. and Strom, T. B., Intragraft IL-15 transcripts are increased in human renal allograft rejection. Transplantation 1996. 62: 543545.
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    Baan, C. C., Niesters, H. G., Metselaar, H. J., Mol, W. M., Loonen, E. H., Zondervan, P. E., Tilanus, H. W. et al., Increased intragraft IL-15 mRNA expression after liver transplantation. Clin. Transplant. 1998. 12: 212218.
  • 45
    Shinozaki, M., Hirahashi, J., Lebedeva, T., Liew, F. Y., Salant, D. J., Maron, R. and Kelley, V. R., IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis. J. Clin. Invest. 2002. 109: 951960.
  • 46
    Vetuschi, A., Latella, G., Sferra, R., Caprilli, R. and Gaudio, E., Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats. Dig. Dis. Sci. 2002. 47: 14471457.
  • 47
    Strater, J., Wellisch, I., Riedl, S., Walczak, H., Koretz, K., Tandara, A., Krammer, P. H. et al., CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology 1997. 113: 160167.
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    Nishiyama, R., Sakaguchi, T., Kinugasa, T., Gu, X., MacDermott, R. P., Podolsky, D. K. and Reinecker, H. C., Interleukin-2 receptor beta subunit-dependent and -independent regulation of intestinal epithelial tight junctions. J. Biol. Chem. 2001. 276: 3557135580.
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    Wherry, E. J., Becker, T. C., Boone, D., Kaja, M. K., Ma, A. and Ahmed, R., Homeostatic proliferation but not the generation of virus specific memory CD8 T cells is impaired in the absence of IL-15 or IL-15Ralpha. Adv. Exp. Med. Biol. 2002. 512: 165175.
  • 50
    Obermeier, F., Dunger, N., Strauch, U. G., Hofmann, C., Bleich, A., Grunwald, N., Hedrich, H. J. et al., CpG motifs of bacterial DNA essentially contribute to the perpetuation of chronic intestinal inflammation. Gastroenterology 2005. 129: 913927.
  • 51
    Yoshihara, K., Yajima, T., Kubo, C. and Yoshikai, Y., Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice. Gut 2006. 55: 334341.
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    Inoue, S., Matsumoto, T., Iida, M., Mizuno, M., Kuroki, F., Hoshika, K. and Shimizu, M., Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlation with disease activity. Am. J. Gastroenterol. 1999. 94: 24412446.
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    Bitton, A., Peppercorn, M. A., Antonioli, D. A., Niles, J. L., Shah, S., Bousvaros, A., Ransil, B. et al., Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology 2001. 120: 1320.
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    Maiuri, L., Ciacci, C., Ricciardelli, I., Vacca, L., Raia, V., Auricchio, S., Picard, J. et al., Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 2003. 362: 3037.
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    Di Sabatino, A., Ciccocioppo, R., Cupelli, F., Cinque, B., Millimaggi, D., Clarkson, M. M., Paulli, M. et al., Epithelium-derived interleukin-15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity and survival in coeliac disease. Gut 2005. 55: 469477.
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    Yu, Y., Sitaraman, S. and Gewirtz, A. T., Intestinal epithelial cell regulation of mucosal inflammation. Immunol. Res. 2004. 29: 5568.
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    Cobrin, G. M. and Abreu, M. T., Defects in mucosal immunity leading to Crohn's disease. Immunol. Rev. 2005. 206: 277295.
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    Wei, X., Orchardson, M., Gracie, J. A., Leung, B. P., Gao, B., Guan, H., Niedbala, W. et al., The Sushi domain of soluble IL-15 receptor alpha is essential for binding IL-15 and inhibiting inflammatory and allogenic responses in vitro and in vivo. J. Immunol. 2001. 167: 277282.
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    Liew, F. Y. and McInnes, I. B., Role of interleukin 15 and interleukin 18 in inflammatory response. Ann. Rheum. Dis. 2002. 61 Suppl 2: 100102.
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    Neurath, M. F., Weigmann, B., Finotto, S., Glickman, J., Nieuwenhuis, E., Iijima, H., Mizoguchi, A. et al., The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J. Exp. Med. 2002. 195: 11291143.
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