IL-12 Up-Regulates IL-18 Receptor Expression on T Cells, Th1 Cells, and B Cells: Synergism with IL-18 for IFN-γ Production

Journal of Immunology - Tập 161 Số 7 - Trang 3400-3407 - 1998
Tomohiro Yoshimoto1,2, Kiyoshi Takeda3, Takashi Tanaka3, Kazunobu Ohkusu1, Shin‐ichiro Kashiwamura2, Haruki Okamura2, Shizuo Akira3, Kenji Nakanishi1,2
1*Department of Immunology and Medical Zoology,
2†Laboratory of Host Defenses, Institute for Advanced Medical Sciences, and
3‡Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

Tóm tắt

AbstractIL-18 is a product of macrophages and with IL-12 strikingly induces IFN-γ production from T, B, and NK cells. Furthermore, IL-18 and IL-12 synergize for IFN-γ production from Th1 cells, although this combination fails to affect Th2 cells. In this study, we show that IL-12 and IL-18 promptly and synergistically induce T and B cells to develop into IFN-γ-producing cells without engaging their Ag receptors. We also studied the mechanism underlying differences in IL-18 responsiveness between Th1 and Th2 cells. Pretreatment of T or B cells with IL-12 rendered them responsive to IL-18, which induces cell proliferation and IFN-γ production. These IL-12-stimulated cells had both high and low affinity IL-18R and an increased IL-18R mRNA expression. In particular, IL-12-stimulated T cells strongly and continuously expressed IL-18R mRNA. However, when T cells developed into Th1 cells after stimulation with anti-CD3 and IL-12, they lowered this IL-12-induced-IL-18R mRNA expression. Then, such T cells showed a dominant response to anti-CD3 by IFN-γ production when they were subsequently stimulated with anti-CD3 and IL-18. In contrast, Th2 cells did not express IL-18R mRNA and failed to produce IFN-γ in response to anti-CD3 and IL-18, although they produced a substantial amount of IFN-γ in response to anti-CD3 and IL-12. However, when Th1 and Th2 cells were stimulated with anti-CD3, IL-12, and IL-18, only the Th1 cells markedly augmented IFN-γ production in response to IL-18, suggesting that IL-18 responsiveness between Th1 and Th2 cells resulted from their differential expression of IL-18R.

Từ khóa


Tài liệu tham khảo

H., Okamura, H. Tsutsui, T. Komatsu, M. Yutsudo, A. Hakura, T. Tanimoto, K. Torigoe, T. Okura, Y. Nukada, K. Hattori, et al 1995. Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 378: 88

Y., Gu, K. Kuida, H. Tsutsui, G. Ku, K. Hsiao, M. A. Fleming, N. Hayashi, K. Higashino, H. Okamura, K. Nakanishi, et al 1997. Activation of interferon-γ inducing factor mediated by interleukin-1β converting enzyme. Science 275: 206

Ghayur, T., S. Banerjee, M. Hugunin, D. Butler, L. Herzog, A. Carter, L. Quintal, L. Sekut, R. Talanian, M. Paskind, W. Wong, R. Kamen, D. Tracey, H. Allen. 1997. Caspase-1 processed IFN-γ-inducing factor and regulates LPS-induced IFN-γ production. Nature 386: 617

S., Ushio, M. Namba, T. Okura, K. Hattori, Y. Nukada, K. Akita, F. Tanabe, K. Konishi, M. Micallef, M. Fujii, et al 1996. Cloning of the cDNA for human IFN-γ-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J. Immunol. 156: 4274

Matsui, K., T. Yoshimoto, H. Tsutsui, Y. Hyodo, N. Hayashi, K. Hiroishi, N. Kawada, H. Okamura, K. Nakanishi, K. Higashino. 1997. Propionibacterium acnes treatment diminishes CD4+NK1.1+ T cells but induces type 1 T cells in the liver by induction of IL-12 and IL-18 production from Kupffer cells. J. Immunol. 159: 97

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

Kohno, K., J. Kataoka, T. Ohtsuki, Y. Suemoto, I. Okamoto, M. Usui, M. Ikeda, M. Kurimoto. 1997. IFN-γ-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J. Immunol. 158: 1541

Tsutsui, H., K. Matsui, N. Kawada, Y. Hyodo, N. Hayashi, H. Okamura, K. Higashino, K. Nakanishi. 1997. IL-18 accounts for both TNF-α- and FasL-mediated hepatotoxic pathways in endotoxin-induced liver injury. J. Immunol. 159: 3961

Dao, T., K. Ohashi, T. Kayano. 1996. Interferon-γ-inducing factor, a novel cytokine, enhances fas ligand mediated cytotoxity of murine T helper 1 cells. Cell. Immunol. 173: 230

Tsutsui, H., K. Nakanishi, K. Matsui, K. Higashino, H. Okamura, Y. Miyazawa, K. Kaneda. 1996. Interferon-γ-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. J. Immunol. 157: 3967

Mosmann, T. R., H. Cherwinski, M. W. Bond, M. A. Giedlin, R. L. Coffman. 1986. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136: 2348

Sher, A., R. L. Coffman. 1992. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu. Rev. Immunol. 10: 385

Abbas, A. K., K. M. Murphy, A. Sher. 1996. Functional diversity of helper T lymphocytes. Nature 383: 787

Swain, S. L., A. D. Weinberg, M. English, G. Huston. 1990. IL-4 directs the development of Th2-like helper effectors. J. Immunol. 145: 3796

Le Gros, G., S. Z. Ben-Sasson, R. A. Seder, F. D. Finkelman, W.E. Paul. 1990. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J. Exp. Med. 172: 921

Seder, R. A., W. E. Paul, M. M. Davis, B. Fazekas de St. Groth.. 1992. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. J. Exp. Med. 176: 1091

Hsieh, C. S., A. B. Heimberger, J. S. Gold, A. O’Garra, K. M. Murphy. 1992. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an αβ T-cell-receptor transgenic system. Proc. Natl. Acad. Sci. USA 89: 6065

Seder, R. A., R. Gazzinelli, A. Sher, W. E. Paul. 1993. Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc. Natl. Acad. Sci. USA 90: 10188

Hsieh, C. S., S. E. Macatonia, C. S. Tripp, S. F. Wolf, A. O’Garra, K. M. Murphy. 1993. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260: 547

Seder, R. A., W. E. Paul. 1994. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu. Rev. Immunol. 12: 635

O’Garra, A., K. M. Murphy. 1994. Role of cytokines in determining T-lymphocyte function. Curr. Opin. Immunol. 6: 458

Trinchieri, G.. 1995. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific and adaptive immunity. Annu. Rev. Immunol. 13: 251

Robinson, D., K. Shibuya, A. Mui, F. Zonin, E. Murphy, T. Sana, S. B. Hartley, S. Menon, R. Kastelein, F. Bazan, A. O’Garra. 1997. IGIF dose not drive Th1 development but synergizes with IL-12 for Interferon-γ production and activates IRAK and NFκB. Immunity 7: 571

Takeda, K., H. Tsutsui, T. Yoshimoto, O. Adachi, N. Yoshida, T. Kishimoto, O. Okamura, K. Nakanishi, S. Akira. 1998. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 8: 383

Ahn, H.-J., S. Maruo, M. Tomura, J. Mu, T. Hamaoka, K. Nakanishi, S. Clark, M. Kurimoto, H. Okamura, H. Fujiwara. 1997. A mechanism underlying synergy between IL-12 and IFN-γ-inducing factor in enhanced production of IFN-γ. J. Immunol. 159: 2125

Torigoe, K., S. Ushio, T. Okura, S. Kobayashi, M. Taniai, T. Kinikata, T. Murakami, O. Sanou, H. Kojima, M. Fuji, T. Ohta, M. Ikeda, H. Ikegami, M. Kurimoto. 1997. Purification and characterization of the human Interleukin-18 (hIL-18) receptor. J. Biol. Chem. 272: 25737

Parnet, P., K. E. Garka, T. P. Bonnet, S. K. Dower, J. E. Sim. 1996. IL-1Rrp is a novel receptor-like molecule similar to the type I Interleukin-1 receptor and its homologues T1/ST2 and IL-1R Acp. J. Biol. Chem. 271: 3967

Leo, O., M. Foo, D. H. Sachs, L. E. Samelson, J. A. Bluestone. 1987. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc. Natl. Acad. Sci. USA 84: 1374

Nakanishi, K., S. Hirose, T. Yoshimoto, H. Ishizashi, K. Hiroishi, T. Tanaka, T. Kono, M. Miyasaka, T. Taniguchi, K. Higashino. 1992. Role and regulation of interleukin (IL)-2 receptor α and β chains in IL-2-driven B-cell growth. Proc. Natl. Acad. Sci. USA 89: 3551

Hu-Li, J., J. Ohara, C. Watson, W. Tsang, W. E. Paul. 1989. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S). J. Immunol. 142: 800

Robb, R. J., A. Munk, K. A. Smith. 1981. T cell growth factor receptors: quantitation, specificity, and biological relevance. J. Exp. Med. 154: 1455

Nakanishi, K., T. Hashimoto, K. Hiroishi, K. Matsui, T. Yoshimoto, H. 3. Morse, J. Furuyama, T. Hamaoka, K. Higashino, W. E. Paul. 1987. Demonstration of up-regulated IL 2 receptor expression on an in vitro cloned BCL1 subline. J. Immunol. 138: 1817

Yoshimoto, T., W. E. Paul. 1994. CD4pos, NK1.1pos T cells promptly produce Interleukin 4 in response to in vivo challenge with anti-CD3. J. Exp. Med. 179: 1285

Emmel, E. A., C. L. Verweij, D. B. Durand, K. M. Higgins, E. Lacy, G. R. Crabtree. 1989. Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science 246: 1617

Zhang, T., K. Kawakami, M. H. Qureshi, H. Okamura, M. Kurimoto, A. Saito. 1997. Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells. Infect. Immun. 65: 3594

Presky, D. H., Y. Hong, L. J. Minetti, A. O. Chua, N. Nabavi, C-Y. Wu, M. K. Gately, U. Gubler. 1996. A functional interleukin 12 receptor complex is composed of two β-type cytokine receptor subunits. Proc. Natl. Acad. Sci. USA 93: 14002

Szabo, S. J., A. S. Dighe, U. Gubler, K. M. Murphy. 1997. Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J. Exp. Med. 185: 817

Jacobson, N. G., S. J. Szabo, R. M. Weber-Nordt, Z. Zhong, R. D. Schreiber, J. E. J. Darnell, K. M. Murphy. 1995. Interleukin 12 signaling in T helper type 1 (Th1) cells involves phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J. Exp. Med. 181: 1755

Szabo, S. J., N. G. Jacobson, A. S. Dighe, U. Gubler, K. M. Murphy. 1995. Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 2: 665

Thierfelder, W. E., J. M. van Deursen, K. Yamamoto, R. A. Tripp, S. R. Sarawar, R. T. Carson, M. Y. Sangster, D. A. A. Vignali, P. C. Doherty, G. C. Grosveld., J. N. Ihle. 1996. Requirement of Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature 382: 171

Kaplan, N. H., Y. L. Sun, T. Hoey, M. J. Grusby. 1996. Impaired IL-12 responses and enhanced development of Th2 cells in STAT4-deficient mice. Nature 382: 174

Matsumoto, S., K. Tsuji-Takayama, Y. Aizawa, K. Koide, M. Takeuchi, T. Ohta, M. Kurimoto. 1997. Interleukin-18 activates NF-κB in murine T helper type 1 cells. Biochem. Biophys. Res. Commun. 234: 454

Hu-Li, J., H. Huang, J. Ryan, W. E. Paul. 1997. In differentiated CD4+ T cells, interleukin 4 production is cytokine-autonomous, whereas interferon γ production is cytokine-dependent. Proc. Natl. Acad. Sci. USA 94: 3189

Manetti, R., F. Gerosa, M. G. Giudizi, R. Biagiotti, P. Parronchi, M. P. Piccinni, S. Sampognaro, E. Maggi, S. Romagnani, G. Trinchieri.. 1994. Interleukin 12 induces stable priming for interferon gamma (IFN-γ) production during differentiation of human T helper (Th) cells and transient IFN-γ production in established Th2 cell clones. J. Exp. Med. 179: 1273

Yssel, H., S. Fasler, J. E. De Vries, R. de Waal Malefyt. 1994. IL-12 transiently induces IFN-γ transcription and protein synthesis in human CD4+ allergen-specific Th2 T cell clones. Int. Immunol. 6: 1091

Thông tin
Thông tin xuất bản

Journal of Immunology

Tập 161 Số 7

3400-3407

Thông tin tác giả