Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon γ, nitric oxide, and apoptosis

Journal of Experimental Medicine

Volumn 189, Issue 2, 1999, Pages 219-230

  Tarrant, Teresa K ^a   Silver, Phyllis B ^a   Wahlsten, Jennifer L ^a   Rizzo, Luiz V ^a   Chan, Chi Chao ^a   Wiggert, Barbara ^b   Caspi, Rachel R ^a,b  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b NATIONAL EYE INSTITUTE   (United States)

Author keywords

Apoptosis; Autoimmune disease; Interleukin 12; T helper type 1; Uveitis

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 5; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PROTEIN BCL 2; RETINA ANTIGEN; RETINOID BINDING PROTEIN;

ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY BLOOD LEVEL; APOPTOSIS; ARTICLE; AUTOIMMUNE DISEASE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DELAYED HYPERSENSITIVITY; FEMALE; HELPER CELL; HISTOPATHOLOGY; IMMUNITY; IMMUNIZATION; IMMUNOLOGICAL TOLERANCE; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE; UVEITIS;

ANIMALS; APOPTOSIS; AUTOIMMUNE DISEASES; EYE PROTEINS; HYPERSENSITIVITY, DELAYED; IMMUNOGLOBULIN G; IN SITU NICK-END LABELING; INTERFERON TYPE II; INTERLEUKIN-12; INTERLEUKIN-5; LYMPH NODES; LYMPHOCYTES; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE TYPE II; PROTO-ONCOGENE PROTEINS C-BCL-2; RETINOL-BINDING PROTEINS; T-LYMPHOCYTES, HELPER-INDUCER; UVEITIS;

EID: 0033579881     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.189.2.219     Document Type: Article

References (68)

1. Caspi, R.R., F.G. Roberge, C.G. McAllister, M. el-Saied, T. Kuwabara, I. Gery, E. Hanna, and R.B. Nussenblatt. 1986. T cell lines mediating experimental autoimmune uveoretinitis (EAU) in the rat J. Immunol. 136:928-933.
2. Gery, I., M. Mochizuki, and R.B. Nussenblatt. 1986. Retinal specific antigens and immunopathogenic processes they provoke. In Progress in Retinal Research. N.N. Osborne and G.J. Chader, editors. Pergamon Press, Oxford. 75-109.
3. Sanui, H., T.M. Redmond, S. Kotake, B. Wiggert, L.H. Hu, H. Margalit, J.A. Berzofsky, G.J. Chader, and I. Gery. 1989. Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP). J. Exp. Med. 169:1947-1960.
4. + T cell line and clone that induce experimental autoimmune uveoretinitis in B10.A mice. J. Immunol. 156:1654-1660.
5. Wolf, S.F., P.A. Temple, M. Kobayashi, D. Young, M. Dicig, L. Lowe, R. Dzialo, L. Fitz, C. Ferenz, R.M. Hewick, et al., 1991. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J. Immunol. 146: 3074-3081.
6. Schoenhaut, D.S., A.O. Chua, A.G. Wolitzky, P.M. Quinn, C.M. Dwyer, W. McComas, P.C. Familletti, M.K. Gately, and U. Gubler. 1992. Cloning and expression of murine IL-12. J. Immunol. 148:3433-3440.
7. Cella, M., D. Scheidegger, K. Palmer-Lehmann, P. Lane, A. Lanzavecchia, and G. Alber. 1996. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 184:747-752.
8. Koch, F., U. Stanzl, P. Jennewein, K. Janke, C. Heufler, E. Kampgen, N. Romani, and G. Schuler. 1996. High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J. Exp. Med. 184:741-746.
9. + T cells through IL-12 produced by Listeria-induced macrophages. Science. 260:547-549.
10. Germann, T., M.K. Gately, D.S. Schoenhaut, M. Lohoff, F. Mattner, S. Fischer, S.C. Jin, E. Schmitt, and E. Rude. 1993. Interleukin-12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells. Eur. J. Immunol. 23:1762-1770.
11. + T cells. J. Immunol. 154:5071-5079.
12. + T cells. Eur. J. Immunol. 24:343-347.
13. Afonso, L.C., T.M. Scharton, L.Q. Vieira, M. Wysocka, G. Trinchieri, and P. Scott. 1994. The adjuvant effect of interleukin-12 in a vaccine against Leishmania major. Science. 263: 235-237.
14. Heinzel, F.P., D.S. Schoenhaut, R.M. Rerko, L.E. Rosser, and M.K. Gately. 1993. Recombinant interleukin 12 cures mice infected with Leishmania major. J. Exp. Med. 177:1505-1509.
15. Schijns, V.E., B.L. Haagmans, and M.C. Horzinek. 1995. IL-12 stimulates an antiviral type 1 cytokine response but lacks adjuvant activity in IFN-gamma-receptor-deficient mice. J. Immunol, 155:2525-2532.
16. McKnight, A.J., G.J. Zimmer, I. Fogelman, S.F. Wolf, and A.K. Abbas. 1994. Effects of IL-12 on helper T cell-dependent immune responses in vivo. J. Immunol. 152:2172-2179.
17. Manetti, R., P. Parronchi, M.G. Giudizi, M.P. Piccinni, E. Maggi, G. Trinchieri, and S. Romagnani. 1993. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J. Exp. Med. 177:1199-1204.
18. Manetti, R., F. Gerosa, M.G. Giudizi, R. Biagiotti, P. Parronchi, M.P. Piccinni, S. Sampognaro, E. Maggi, S. Romagnani, G. Trinchieri, et al. 1994. Incerleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones. J. Exp. Med. 179:1273-1283.
19. + T cell clones from HIV-infected patients. J. Clin. Invest. 96:1677-1682.
20. Gerosa, F., C. Paganin, D. Peritt, F. Paiola, M.T. Scupoli, M. Aste-Amezaga, I. Frank, and G. Trinchieri. 1996. Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin 10. J. Exp. Med. 183:2559-2569.
21. Mosmann, T.R., H. Cherwinski, M.W. Bond, M.A. Giedlin, and 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. 136:2348-2357.
22. Caspi, R.R., P.B. Silver, C.C. Chan, B. Sun, R.K. Agarwal, J. Wells, S. Oddo, Y. Fujino, F. Najafian, and R.L. Wilder. 1996. Genetic susceptibility to experimental autoimmune uveoretinitis in the rat is associated with an elevated Th1 response. J. Immunol. 157:2668-2675.
23. Sun, B., L.V. Rizzo, S.-H. Sun, C.-C. Chan, B. Wiggert, R.L. Wilder, and R.R. Caspi. 1997. Genetic susceptibility to experimental autoimmune uveitis involves more than a predisposition to generate a T helper-1-like or a T helper-2-like response. J. Immunol. 159:1004-1011.
24. Tarrant, T.K., P.B. Silver, C.C. Chan, B. Wiggert, and R.R. Caspi. 1998. Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis. J. Immunol. 161:122-127.
25. Dalton, D.K., S. Pitts-Meek, S. Keshav, I.S. Figari, A. Bradley, and T.A. Stewart. 1993. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 259:1739-1742.
26. MacMicking, J.D., C. Nathan, G. Horn, N. Chartrain, D.S. Fletcher, M. Trumbauer, K. Stevens, Q.W. Xie, K. Sokol, N. Hutchinson, et al. 1995. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase [published erratum appears in Cell. 1995. 81: following 1170]. Cell. 81:641-650.
27. Sentman, C.L., J.R. Shutter, D. Hockenbery, O. Kanagawa, and S.J. Korsmeyer. 1991. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell. 67: 879-888.
28. Pepperberg, D.R., T.L. Okajima, H. Ripps, G.J. Chader, and B. Wiggert. 1991. Functional properties of interphotoreceptor retinoid-binding protein. Photochem. Photobiol. 54: 1057-1060.
29. Chan, C.C., R.R. Caspi, M. Ni, W.C. Leake, B. Wiggert, G.J. Chader, and R.B. Nussenblatt. 1990. Pathology of experimental autoimmune uveoretinitis in mice. J. Autoimmun. 3:247-255.
30. Rizzo, L.V., N.E. Miller-Rivero, C.C. Chan, B. Wiggert, R.B. Nussenblatt, and R.R. Caspi. 1994. Interleukin 2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity. J. Clin. Invest. 94:1668-1672.
31. Rizzo, L.V., R.H. DeKruyff, D.T. Umetsu, and R.R. Caspi. 1995. Regulation of the interaction between Th1 and Th2 T cell clones to provide help for antibody production in vivo. Eur. J. Immunol. 25:708-716.
32. Snedecor, G.W., and W.G. Cochran. 1967. Statistical Methods. Iowa State University Press, Ames, IA. p. 248.
33. Caspi, R.R., B.G. Grubbs, C.C. Chan, G.J. Chader, and B. Wiggert. 1992. Genetic control of susceptibility to experimental autoimmune uveoretinitis in the mouse model: concomitant regulation by MHC and non-MHC genes. J. Immunol. 148:2384-2389.
34. Caspi, R.R., C.C. Chan, B.G. Grubbs, P.B. Silver, B. Wiggert, C.F. Parsa, S. Bahmanyar, A. Billiau, and H. Heremans. 1994. Endogenous systemic IFN-gamma has a protective role against ocular autoimmunity in mice. J. Immunol. 152:890-899.
35. Jones, L.S., L.V. Rizzo, R.K. Agarwal, T.K. Tarrant, C.C. Chan, B. Wiggerrt, and R.R. Caspi. 1997. Interferon gamma-deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response. J. Immunol. 158:5997-6005.
36. Windhagen, A., D.E. Anderson, A. Carrizosa, R.E. Williams, and D.A. Hafler. 1996. IL-12 induces human T cells secreting IL-10 with IFN-gamma. J. Immunol. 157:1127-1131.
37. + T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J. Immunol. 157:798-805.
38. Berg, D.J., N. Davidson, R. Kuhn, W. Muller, S. Menon, G. Holland, L. Thompson-Snipes, M.W. Leach, and D. Rennick. 1996. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J. Clin. Invest. 98: 1010-1020.
39. Xie, K., Y. Wang, S. Huang, L. Xu, D. Bielenberg, T. Salas, D.J. McConkey, W. Jiang, and I.J. Fidler. 1997. Nitric oxide-mediated apoptosis of K-1735 melanoma cells is associated with downregulation of Bcl-2. Oncogene. 15:771-779.
40. Xie, K., S. Huang, Y. Wang, P.J. Beltran, S.H. Juang, Z. Dong, J.C. Reed, T.J. McDonnell, D.J. McConkey, and I.J. Fidler. 1996. Bcl-2 protects cells from cytokine-induced nitric-oxide-dependent apoptosis. Cancer Immunol. Immunother. 43:109-115.
41. Messmer, U.K., U.K. Reed, and B. Brune. 1996. Bcl-2 protects macrophages from nitric oxide-induced apoptosis. J. Biol. Chem. 271:20192-20197.
42. Melkova, Z., S.B. Lee, D. Rodriguez, and M. Esteban. 1997. Bcl-2 prevents nitric oxide-mediated apoptosis and poly (ADP-ribose) polymerase cleavage. FEBS (Fed. Eur. Biochem. Soc.) Lett. 403:273-278.
43. Trembleau, S., T. Germann, M.K. Gately, and L. Adorini. 1995. The role of IL-12 in the induction of organ-specific autoimmune diseases. Immunol. Today. 16:383-386.
44. Leonard, J.P., K.E. Waldburger, and S.J. Goldman. 1995. Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. J. Exp. Med. 181:381-386.
45. Waldburger, K.E., R.C. Hastings, R.G. Schaub, S.J. Goldman, and J.P. Leonard. 1996. Adoptive transfer of experimental allergic encephalomyelitis after in vitro treatment with recombinant murine interleukin-12. Preferential expansion of interferon-gamma-producing cells and increased expression of macrophage-associated inducible nitric oxide synthase as immunomodulatory mechanisms. Am. J. Pathol. 148: 375-382.
46. Germann, T., J. Szeliga, H. Hess, S. Storkel, F.J. Podlaski, 1M.K. Gately, E. Schmitt, and E. Rude. 1995. Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice. Proc. Natl. Acad. Sci. USA. 92:4823-4827.
47. Billiau, A., H. Heremans, F. Vandekerckhove, R. Dijkmans, H. Sobis, E. Meulepas, and H. Carton. 1988. Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J. Immunol. 140:1506-1510.
48. Rizzo, L.V., H. Xu, C.C. Chan, B. Wiggert, and R.R. Caspi. 1998. IL-10 has a protective role in experimental autoimmune uveoretinitis. Int. Immunol. 10:807-814.
49. Willenborg, D.O., S. Fordham, C.C.A. Bernard, W.B. Cowden, and I.A. Ramshaw. 1996. IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J. Immunol. 157:3223-3227.
50. Sveinbjornsson, B., R. Olsen, O.M. Seternes, and R. Seljelid. 1996. Macrophage cytotoxicity against murine meth A sarcoma involves nitric oxide-mediated apoptosis. Biochem. Biophys. Res. Commun. 223:643-649.
51. Geng, Y.J., Q. Wu, M. Muszynski, G.K. Hansson, and P. Libby. 1996. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Arterioscler. Thromb. Vasc. Biol. 16:19-27.
52. Bauer, H., T. Jung, D. Tsikas, D.O. Stichtenoth, J.C. Frolich, and C. Neumann. 1997. Nitric oxide inhibits the secretion of T-helper 1- and T-helper 2-associated cytokines in activated human T cells. Immunology. 90:205-211.
53. Geng, Y.J., K. Hellstrand, A. Wennmalm, and G.K. Hansson. 1996. Apoptotic death of human leukemic cells induced by vascular cells expressing nitric oxide synthase in response to gamma-interferon and tumor necrosis factor-alpha. Cancer Res. 56:866-874.
54. Han, X., K. Becker, H.J. Degen, H. Jablonowski, and G. Strohmeyer. 1996. Synergistic stimulatory effects of tumour necrosis factor alpha and interferon gamma on replication of human immunodeficiency virus type 1 and on apoptosis of HIV-1-infected host cells. Eur. J. Clin. Invest. 26:286-292.
55. Iwahashi, H., T. Hanafusa, Y. Eguchi, H. Nakajima, J. Miyagawa, N. Itoh, K. Tomita, M. Namba, M. Kuwajima, T. Noguchi, et al. 1996. Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2. Diabetologia. 39:530-536.
56. Jo, T., T. Tomiyama, K. Ohashi, F. Saji, O. Tanizawa, M. Ozaki, R. Yamamoto, T. Yamamoto, Y. Nishizawa, and N. Terada. 1995. Apoptosis of cultured mouse luteal cells induced by tumor necrosis factor-alpha and interferon-gamma. Anat. Rec. 241:70-76.
57. Levy-Strumpf, N., L.P. Deiss, H. Berissi, and A. Kimchi. 1997. DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death. Mol. Cell Biol. 17:1615-1625.
58. Brysk, M.M., P. Selvanayagam, I. Arany, H. Brysk, S.K. Tyring, and S. Rajaraman. 1995. Induction of apoptotic nuclei by interferon-gamma and by predesquamin in cultured keratinocytes. J. Interferon Cytokine. Res. 15:1029-1035.
59. Maier, J.A., D. Morelli, and A. Balsari. 1995. The differential response to interferon gamma by normal and transformed endothelial cells. Biochem. Biophys. Res. Commun. 214:582-588.
60. Trubiani, O., D. Bosco, and R. Di Primio. 1994. Interferon-gamma (IFN-gamma) induces programmed cell death in differentiated human leukemic B cell lines. Exp. Cell. Res. 215: 23-27.
61. Gold, D.P., K. Schroder, H.C. Powell, and C.J. Kelly. 1997. Nitric oxide and the immunomodulation of experimental allergic encephalomyelitis. Eur. J. Immunol. 27:1-7.
62. Fenyk-Melody, J.E., A.E. Garrison, S.R. Brunnert, J.R. Weidner, F. Shen, B.A. Shelton, and J.S. Mudgett. 1998. Experimental autoimmune encephalomyelitis is exacerbated in mice lacking the NOS2 gene. J. Immunol. 160:2940-2946.
63. Krakowski, M., and T. Owens. 1996. Interferon-γ confers resistance to experimental allergic encephalomyelitis. Eur. J. Immunol. 26:1641-1646.
64. Whitcup, S.M., L.V. Rizzo, J.C. Lai, S. Hayashi, R. Gazzinelli, and C.C. Chan. 1996. IL-12 inhibits endotoxin-induced inflammation in the eye. Eur. J. Immunol. 26:995-999.
65. Hess, H., M.K. Gately, E. Rude, E. Schmitt, J. Szeliga, and T. Germann. 1996. High doses of interleukin-12 inhibit the development of joint disease in DBA/1 mice immunized with type II collagen in complete Freund's adjuvant. Eur. J. Immunol. 26:187-191.
66. Szeliga, J., H. Hess, E. Rude, E. Schmitt, and T. Germann. 1996. IL-12 promotes cellular but not humoral type II collagen-specific Th 1-type responses in C57BL/6 and B10.Q mice and fails to induce arthritis. Int. Immunol. 8:1221-1227.
67. O'Hara, R.M., Jr., S.L. Henderson, and A. Nagelin. 1996. Prevention of a Th1 disease by a ThI cytokine: IL-12 and diabetes in NOD mice. Ann. NY Acad. Sci. 795:241-249.
68. Xu, H., L.V. Rizzo, P.B. Silver, and R.R. Caspi. 1997. Uveitogenicity is associated with a Th1-like lymphokine profile: cytokine-dependent modulation of primary and committed T cells in EAU. Cell. Immunol. 178:69-78.