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Leading Article

Selective Immunointervention in Autoimmune Diseases: Lessons from Multiple Sclerosis

Pages 219-234 | Published online: 18 Jul 2013

References

  • Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci USA 1992; 89: 421–425.
  • Chen Y, Kuchroo VK, Inobe J-I, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppres-sion of autoimmune encephalomyelitis. Science 1994; 265: 1237–1240.
  • Weiner HL, Friedman A, Miller A, et al. Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu Rev Immunol 1994; 12: 809–837.
  • Lehmann P, Sercarz E, Forsthuber T, Dayan C, Gammon G. Determinant spreading and the dynamics of the autoimmune T cell repertoire. Immunol Today 1993; 14: 203–208.
  • Garcia G, Weiner HL. Manipulation of Th responses by oral tolerance. Curr Top Microbiol Immunol 1999; 238: 123–145.
  • Chen Y, Inobe J-I, Marks R, GonneIla P, Kuchroo VK, Weiner HL. Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature 1995; 376: 177–180.
  • Marth T, Zeitz M, Ludviksson BR, Strober W, Kelsall BL. Extinction of IL-12 signaling promotes Fas-mediated apoptosis of antigen-specific T cells. J Immunol 1999; 162: 7233-7240.
  • Khoury SJ, Hancock WW, Weiner HL. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregu-lation of inflammatory cytokines and differential upregulation of transforming growth factor 13, interleukin 4, and prostaglandin E expression in the brain. J Exp Med 1992; 176: 1355-1364.
  • Weinberg AD, Whitham R, Swain SL, et al. Transforming growth factor beta enhances the in vivo effector function and memory phenotype of antigen-specific T helper cells in experimental autoimmune encephalomyelitis. J Immunol 1992; 148: 2109–2117.
  • Metzler B, Wraith DC. Inhibition of experimental autoimmune encephalitis by inhalation but not by oral admin-istration of encephalitogenic peptide: influence of MHC bind-ing. Int Immunol 1992; 5: 1159–1165.
  • Weiner HL, Mackin GA, Matsui M, et al. Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. Science 1993; 259: 1321–1324.
  • Barnett ML, Kremer JM, St. Clair EW, et al. Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial [published erratum appears in Arthritis Rheum 1998; 41 (5): 938] [see comments]. Arthritis Rheum 1998; 41: 290–297.
  • Nussenblatt RB, Gery I, Weiner HL, et al. Treatment of uveitis by oral administration of retinal antigens: results of a phase I/II randomized masked trial [see comments]. Am J Ophthalmol 1997; 123: 583–592.
  • Evavold BD, Sloan-Lancaster J, Allen PM. Tickling the TCR: selective T cell functions stimulated by altered peptide ligands. Immunol Today 1993; 14: 602–609.
  • De Magistris TM, Alexander J, Coggeshall M, et al. Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell 1992; 68: 625–634.
  • Jameson SC, Carbone FR, Bevan MJ. Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells. J Exp Med 1993; 177: 1541–1550.
  • Klenerman P, Rowland-Jones S, McAdam S, et al. Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants. Nature 1994; 369: 403–407.
  • Bertoletti A, Sette A, Chisari FV, et al. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antivi-ral cytotoxic T cells. Nature 1994; 369: 407–410.
  • Plebanski M, Flanagan KL, Lee EA, et al. Interleukin 10-mediated immunosuppression by a variant CD4 T cell epi-tope of Plasmodium falciparum. Immunity 1999; 10: 651–660.
  • Plebanski M, Lee EA, Hannan CM, et al. Altered pep-tide ligands narrow the repertoire of cellular immune respons-es by interfering with T-cell priming. Nat Med 1999; 5: 565–571.
  • Anderton SM, Kissler S, Lamont AG, Wraith DC. Therapeutic potential of TCR antagonists is determined by their ability to modulate a diverse repertoire of autoreactive T cells. Eur J Immunol 1999; 29: 1850–1857.
  • Ruiz PJ, Garren H, Hirschberg DL, et al. Microbial epi-topes act as altered peptide ligands to prevent experimental autoimmune encephalomyelitis. J Exp Med 1999; 189: 1275–1284.
  • Karin N, Mitchell DJ, Brocke S, Ling N, Steinman L. Reversal of Experimental Autoimmune Encephalomyelitis by a soluble peptide variant of a myelin basic protein epitope: T cell receptor antagonism and reduction of interferon y and tumor necrosis factor a production. J Exp Med 1994; 180: 2227–2237.
  • Brocke S, Gijbels K, Allegretta M, et al. Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein. Nature 1996; 379: 343–346.
  • Nicholson LB, Greer JM, Sobel RA, Lees MB, Kuchroo VK. An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Immunity 1995; 3: 397–405.
  • Windhagen A, Scholz C, Hollsberg P, Fukaura H, Sette A, Hafler DA. Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity 1995; 2: 373–380.
  • Kappos L, Comi G, Panitch H, et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. Nat Med 2000; 6: 1176-1182.
  • Bielekova B, Goodwin B, Richert N, et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: Results of a phase II clinical trial with an altered peptide ligand. Nat Med 2000; 6: 1167-1175.
  • Aharoni R, Teitelbaum D, Arnon R, Sela M. Copolymer 1 acts against the immunodominant epitope 82-100 of myelin basic protein by T cell receptor antagonism in addition to major histocompatibility complex blocking. Proc Natl Acad Sci USA 1999; 96: 634–639.
  • Johnson KP, Brooks BR, Cohen JA, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group [see comments]. Neurology 1998; 50: 701–708.
  • Lenardo M, Chan K, Hornung F, et al. Mature T lym-phocyte apoptosis-immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev Immunol 1999; 17: 221–253.
  • Siegel RM, Fleisher TA. The role of Fas and related death receptors in autoimmune and other disease states. J Allergy Clin Immunol 1999; 103: 729–738.
  • Zang YC, Kozovska MM, Hong J, et al. Impaired apoptotic deletion of myelin basic protein-reactive T cells in patients with multiple sclerosis. Eur J Immunol 1999; 29: 1692–1700.
  • Critchfield JM, Racke MK, Zuniga-Pflucker JC, et al. T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis. Science 1994; 263: 1139–1143.
  • Ishigami T, White C, Pender M. Soluble antigen thera-py induces apoptosis of autoreactive T cells preferentially in the target organ rather than in the peripheral lymphoid organs. Eur J Immunol 1998; 28: 1623–1635.
  • Elliott E, McFarland H, Nye S, et al. Treatment of experimental encephalomyelitis with a novel chimeric fusion protein of myelin basic protein and proteolipid protein. J Clin Invest 1996; 87: 1602–1612.
  • McFarland H, Lobito A, Johnson M, et al. Determinant spreading associated with demyelination in a nonhuman pri-mate model of multiple sclerosis. J Immunol 1999; 162: 2384–2390.
  • Schwartz RH. A cell culture model for T cell anergy. Science 1990; 248: 1349–1356.
  • Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996; 14: 233–258.
  • Grewal I, Flavell R. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998; 16: 111–135.
  • Walunas TL, Bakker CY, Bluestone JA. CTLA-4 liga-tion blocks CD28-dependent T cell activation. J Exp Med 1996; 183: 2541-2550.
  • Larsen C, Elwood E, Alexander D, et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 1996; 381: 434–438.
  • Kenyon N, Chatzipetrou M, Masetti M, et al. Long-term survival and function of intrahepatic islet allografts in rhe-sus monkeys treated with humanized anti-CD154. Proc Natl Acad Sci USA 1999; 96: 8132-8137.
  • Kirk A, Burkly L, Batty D, et al. Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nature Med 1999; 6: 686–693.
  • Bachmann MF, Speiser DE, Mak TW, Ohashi PS. Absence of co-stimulation and not the intensity of TCR signal-ing is critical for the induction of T cell unresponsiveness in vivo. Eur J Immunol 1999; 29: 2156–2166.
  • Aloisi F, Penna G, Polazzi E, Minghetti L, Adorini L. CD40-CD154 interaction and IFN-y are required for IL-12 but not prostaglandin E2 secretion by microglia during antigen presentation to Thl cells. J Immunol 1999; 162: 1384-1391.
  • Howard LM, Miga AJ, Vanderlugt CL, et al. Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an animal model of multiple scle-rosis. J Clin Invest 1999; 103: 281–290.
  • Kawai T, Andrews D, Colvin RB, Sachs DH, Cosimi AB. Thromboembolic complications after treatment with mon-oclonal antibody against CD40 ligand [In Process Citation]. Nat Med 2000; 6: 114.
  • Karandikar NJ, Vanderlugt CL, Walunas TL, Miller SD, Bluestone JA. CTLA-4: a negative regulator of autoimmune disease. J Exp Med 1996; 184: 783–788.
  • Ruiz PJ, Garren H, Ruiz IU, et al. Suppressive immu-nization with DNA encoding a self-peptide prevents autoim-mune disease: modulation of T cell costimulation. J Immunol 1999; 162: 3336–3341.
  • Abrams JR, Lebwohl MG, Guzzo CA, et al. CTLA4Ig-mediated blockade of T-cell costimulation in patients with pso-riasis vulgaris. J Clin Invest 1999; 103: 1243-1252.
  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffmann RL. Two types of murine helper T cell clone. I Definition according to profile of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348–2357.
  • Del Prete G, De Carli M, Mastromauro C, et al. Purified protein derivative of Mycobacterium tuberculosis and escretory-secretory antigen(s) of Toxocara can is expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest 1991; 88: 346–350.
  • Gately MK, Renzetti LM, Magram J, et al. The inter-leukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol 1998; 16: 495–512.
  • Paul WE, Seder RA. Lymphocytes responses and cytokines. Cell 1994; 76: 241–251.
  • O'Garra A. Cytokines induce the development of func-tionally heterogeneous T helper cell subsets. Immunity 1998; 8: 275–283.
  • Hsieh C-S, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of Thl CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 1993; 260: 547–549.
  • Reiner SL, Locksley RM. The regulation of immunity to Leishmania major. Annu Rev Immunol 1995; 13: 151–177.
  • Romagnani S. Lymphokine production by human T cells in disease states. Annu Rev Immunol 1994; 12: 227–257.
  • Mosmann TR, Sad S. The expanding universe of T-cell subsets: Thl, Th2 and more. Immunol Today 1996; 17: 138–146.
  • Brod SA, Benjamin D, Hafler DA. Restricted T cell expression of IL-2, IFN-y mRNA in human inflammatory dis-ease. J Immunol 1991; 147: 810–815.
  • Windhagen A, Newcombe J, Dangond F, et al. Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med 1995; 182: 1985-1996.
  • Balashov KE, Smith DR, Khoury SJ, Hafler DA, Weiner HL. Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proc Natl Acad Sci USA 1997; 94: 599–603.
  • Comabella M, Balashov K, Issazadeh S, Smith D, Weiner HL, Khoury SJ. Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normal-ized by pulse cyclophosphamide therapy. J Clin Invest 1998; 102: 671–678.
  • Racke MK, Bonomo A, Scott DE, et al. Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. J Exp Med 1994; 180: 1961–1966.
  • Bettelli E, Prabhu Das M, Howard ED, Weiner HL, Sobel RA, Kuchroo VK. IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J Immunol 1998; 161: 3299-3306.
  • Lafaille JJ, Van-de-Keere F, Hsu AL, et al. Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from disease. J Exp Med 1997; 186: 307–312.
  • Genain CP, Abel K, Belmar N, et al. Late complica-tions of immune deviation therapy in a nonhuman primate. Science 1996; 274: 2054–2056.
  • Acha-Orbea H, Mitchell DJ, Timmermann L, et al. Limited heterogeneity of T cell receptors in experimental aller-gic encephalomyelitis. Cell 1988; 54: 263–273.
  • Waisman A, Ruiz PJ, Hirschenberg DL, et al. Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity. Nature Med 1996; 2: 899–905.
  • Mathisen PM, Tuohy VK. Gene therapy in the treat-ment of autoimmune disease. Immunol Today 1998; 19: 103–105.
  • Martino G, Furlan R, Galbiati F, et al. A gene therapy approach to treat demyelinating diseases using non- replicative herpetic vectors engineered to produce cytokines. Mult Scler 1998; 4: 222–227.
  • Dinarello CA. Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 1998; 16: 457–499.
  • Furlan R, Martino G, Galbiati F, et al. Caspase-1 regu-lates the inflammatory process leading to autoimmune demyelination. J Immunol 1999; 163: 2403-2409.
  • Panitch HS, Hirsch RL, Schindler J, Johnson KP. Treatment of multiple sclerosis with gamma interferon: exacer-bations associated with activation of the immune system. Neurology 1987; 37: 1097–1102.
  • Krakowski M, Owens T. Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur J Immunol 1996; 26: 1641–1646.
  • Aloisi F, Penna G, Cerase J, Menêndez Iglesias B, Adorini L. IL-12 production by central nervous system microglia is inhibited by astrocytes. J Immunol 1997; 159: 1604-1612.
  • Manetti R, Parronchi P, Giudizi MG, et al. Natural killer cell stimulatory factor (interleukin 12, IL-12) induces T helper type 1 (Thl)-specific immune responses and inhibits the devel-opment of IL-4-producing Th cells. J Exp Med 1993; 177: 1199-1204.
  • Afonso LCC, Scharton TM, Vieira LQ, Wysocka M, Trinchieri G, Scott P. The adjuvant effect of interleukin-12 in a vaccine against Leishmania major. Science 1994; 263: 235–237.
  • Magram J, Connaughton S, Warner R, et al. IL-12 deficient mice are defective in IFN-y production and type 1 cytokine responses. Immunity 1996; 4: 471–482.
  • Wu C-y, Ferrante J, Gately MK, Magram J. Characterization of IL-12 receptor 131 chain (IL-12R131)-defi-cient mice: IL-12R131 is an essential component of the func-tional mouse IL-12R. J Immunol 1997; 159: 1658-1665.
  • Kaplan MH, Sun Y-L, Hoey T, Grusby MJ. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 1996; 382: 174–177.
  • Trembleau S, Penna G, Bosi E, Mortara A, Gately MK, Adorini L. IL-12 administration induces Thl cells and acceler-ates autoimmune diabetes in NOD mice. J Exp Med 1995; 181: 817–821.
  • Leonard JP, Waldburger KE, Goldman SJ. Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin-12. J Exp Med 1995; 181: 381–386.
  • Germann T, Szeliga J, Hess H, et al. Administration of IL-12 in combination with type II collagen induces severe arthritis in DBA/1 mice. Proc Natl Acad Sci USA 1995; 92: 4823-4827.
  • Xu H, Rizzo LV, Silver PB, Caspi RR. Uveitogenicity is associated with a Thl-like lymphokine profile: cytokine-depen-dent modulation of early and committed effector T cells in experimental autoimmune uveitis. Cell Immunol 1997; 178: 69–78.
  • Neurath MF, Fuss I, Kelsall BL, Stueber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 1995; 182: 1281-1290.
  • Moiola L, Galbiati F, Martino G, et al. IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease. Eur J Immunol 1998; 28: 2487-2497.
  • Zaccone P, Hutchings P, Nicoletti F, Penna G, Adorini L, Cooke A. The involvement of IL-12 in experimentally induced autoimmune thyroid disease. Eur J Immunol 1999; 29: 1933-1942.
  • Morahan G, Huang D, Ymer SI, et al. Linkage disequi-librium of a type 1 diabetes susceptibility locus with a regulato-ry IL12B allele. Nat Genet 2001; 27: 218–221.
  • Adorini L. Interleukin 12 and autoimmune diabetes. Nat Genet 2001; 27: 131–132.
  • Constantinescu CS, Wysocka M, Hilliard B, et al. Antibodies against interleukin-12 prevent superantigen-induced and spontaneous relapses of experimental allergic encephalomyelitis. J Immunol 1998; 161: 5097-5104.
  • Mattner F, Smiroldo S, Galbiati F, et al. Inhibition of Thl development and treatment of chronic-relapsing experi-mental allergic encephalomyelitis by a non-hypercalcemic ana-logue of 1,25-dihydroxyvitamin D(3). Eur J Immunol 2000; 30: 498–508.
  • Ferrante P, Fusi M, Sarasella M, et al. Cytokine pro-duction and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production augmented signal-ing lymphocytic activation molecule (SLAM)-expressing lym-phocytes in acute multiple sclerosis. J Immunol 1998; 160: 1514-1521.
  • Selmaj K, Raine CS. Tumor necrosis factor mediates myelin damage in organotypic cultures of nervous tissue. Ann NY Acad Sci 1988; 540: 568–570.
  • Kuroda Y, Shimamoto Y. Human tumor necrosis fac-tor-alpha augments experimental allergic encephalomyelitis in rats. J Neuroimmunol 1991; 34: 159–164.
  • Baker D, Butler D, Scallon BJ, O'Neill JK, Turk JL, Feldmann M. Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor-immunoglobulin fusion proteins. Eur J Immunol 1994; 24: 2040–2048.
  • Liu J, Marino MW, Wong G, et al. TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyeli-nation. Nature Med 1998; 4: 78–83.
  • van Oosten BW, Barkhof F, Truyen L, et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis fac-tor antibody cA2. Neurology 1996; 47: 1531-1534.
  • TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology 1999; 53: 457–465.
  • Wiendl H, Neuhaus O, Kappos L, Hohlfeld R. Multiple sclerosis. Current review of failed and discontinued clinical tri-als of drug treatment. Nervenarzt 2000; 71: 597–610.
  • Furlan R, Poliani PL, Galbiati F, et al. Central nervous system delivery of interleukin 4 by a nonreplicative herpes simplex type 1 viral vector ameliorates autoimmune demyeli-nation. Hum Gene Ther 1998; 9: 2605-2617.
  • Moore K, O'Garra A, de Waal Malefyt R, Vieira P, Mosmann TR. Interleukin-10. Annu Rev Immunol 1993; 11: 165–190.
  • D' Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon-g production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med 1993; 178: 1041-1048.
  • Fiorentino DF, Zlotnik A, Mosmann TR, Howard MH, O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147: 3815-3622.
  • de Waal Malefyt R, Abrams J, Bennett B, Figdor C, de Vries J. IL-10 inhibits cytokine synthesis by human mono-cytes: an auto-regulatory role of IL-10 produced by mono-cytes. J Exp Med 1991; 174: 1209-1220.
  • Bogdan C, Vodovotz Y, Nathan C. Macrophage deac-tivation by interleukin 10. J Exp Med 1991; 174: 1549-1555.
  • Groux H, Bigler M, De Vries JE, Roncarolo MG. Interleukin-10 induces a long-term antigen specific anergic state in human CD4+ T cells. J Exp Med 1996; 184: 19–29.
  • Cua DJ, Hutchins B, LaFace DM, Stohlman SA, Coffman RL. Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis. J Immunol 2001; 166: 602–608.
  • Martino G, Poliani PL, Furlan R, et al. Cytokine thera-py in immune-mediated demyelinating diseases of the central nervous system: a novel gene therapy approach. J Neuroimmunol 2000; 107: 184–190.
  • Inaba K, Kitaura M, Kato T, Watanabe Y, Kawade Y, Muramatsu S. Contrasting effect of alpha/beta- and gamma-interferons on expression of macrophage Ia antigens. J Exp Med 1986; 163: 1030–1035.
  • Panitch HS, Hirsch RL, Haley AS, Johnson KP. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1987; 1: 893–895.
  • Arnason BG. Immunologic therapy of multiple sclero-sis. Annu Rev Med 1999; 50: 291–302.
  • Jacobs LD, Cookfair DL, Rudick RA, et al. A phase III trial of intramuscular recombinant interferon beta as treatment for exacerbating-remitting multiple sclerosis: design and con-duct of study and baseline characteristics of patients. Multiple Sclerosis Collaborative Research Group (MSCRG). Mult Scler 1995; 1: 118–135.
  • Rep MH, Schrijver HM, van Lopik T, et al. (IFN)-beta treatment enhances CD95 and interleukin 10 expression but reduces interferon-gamma producing T cells in MS patients. J Neuroimmunol 1999; 96: 92–100.
  • Furlan R, Bergami A, Lang R, et al. Interferon-beta treatment in multiple sclerosis patients decreases the number of circulating T cells producing interferon-gamma and inter-leukin-4. J Neuroimmunol 2000; 111: 86–92.
  • Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998; 16: 137–161.
  • Schluesener HJ, Lider O. Transforming growth factors beta 1 and beta 2: cytokines with identical immunosuppressive effects and a potential role in the regulation of autoimmune T cell function. J Neuroimmunol 1989; 24: 249–258.
  • Johns LD, Sriram S. Experimental allergic encephalomyelitis: neutralizing antibody to TGF beta 1 enhances the clinical severity of the disease. J Neuroimmunol 1993; 47: 1–7.
  • McCartney-Francis NL, Frazier-Jessen M, Wahl SM. TGF-beta: a balancing act. Int Rev Immunol 1998; 16: 553–580.
  • Calabresi PA, Fields NS, Maloni HW, et al. Phase 1 trial of transforming growth factor beta 2 in chronic progres-sive MS. Neurology 1998; 51: 289–292.
  • Ben-Nun A, Wekerle H, Cohen IR. Vaccination against autoimmune encephalomyelitis with T-lymphocyte line cells reactive against myelin basic protein. Nature 1981; 292: 60–61.
  • Cohen IR. Regulation of autoimmune disease: physio-logical and therapeutic. Immunol Rev 1986; 94: 5–21.
  • Lider O, Reshef T, Beraud E, Ben-Nun A, Cohen IR. Anti-idiotypic network induced by T cell vaccination against EAE. Science 1989; 239: 181–183.
  • Zhang J, Medaer R, Stinissen P, Hafler D, Raus J. MHC-restricted depletion of human myelin basic protein-reac-tive T cells by T cell vaccination. Science 1993; 261: 1451–1454.
  • Medaer R, Stinissen P, Truyen L, Raus J, Zhang J. Depletion of myelin-basic-protein autoreactive T cells by T-cell vaccination: pilot trial in multiple sclerosis. Lancet 1995; 346: 807–808.
  • Zhang J, Vandevyver C, Stinissen P, Raus J. In vivo clonotypic regulation of human myelin basic protein-reactive T cells by T cell vaccination. J Immunol 1995; 155: 5868–5877.
  • Chunduru SK, Sutherland RM, Stewart GA, Doms RW, Paterson Y. Exploitation of the Vbeta8.2 T cell receptor in protection against experimental autoimmune encephalomyelitis using a live vaccinia virus vector. J Immunol 1996; 156: 4940–4945.
  • Howell MD, Winters ST, Olee T, Powell HC, Carlo DJ, Brosstoff SW. Vaccination against experimental allergic encephalmyelitis with T cell receptor peptides. Science 1989; 246: 668–670.
  • Vandenbark AA, Hashim G, Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature 1989; 341: 541–544.
  • Gaur A, Haspel R, Mayer JP, Fathman CG. Requirement for CD8+ cells in T cell receptor peptide-induced clonal unresponsiveness. Science 1993; 259: 91–94.
  • Offner H, Hashim GA, Vandenbark AA. T cell recep-tor peptide therapy triggers autoregulation of experimental encephalomyelitis. Science 1991; 251: 430–432.
  • Kumar V, Sercarz E. Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine secretion profile of TCR peptide-specific regulatory CD4 T cells. J Immunol 1998; 161: 6585-6591.
  • Kotzin BL, Karuturi S, Chou YK, et al. Preferential T cell receptor VI3 gene usage by myelin basic protein-specific T cell clones from patients with multiple sclerosis. Proc Natl Acad Sci USA 1991; 88: 9161-9165.
  • Satyanarayana K, Chou YK, Bourdette D, et al. Epitope specificity and V gene expression of cerebrospinal fluid T cells specific for intact versus cryptic epitopes of myelin basic protein. J Neuroimmunol 1993; 44: 57–68.
  • Chou YD, Buenafe AC, Dedrick R, et al. T cell recep-tor Vb gene usage in the recognition of myelin basic protein by cerebrospinal fluid-and blood-derived T cells from patients with multiple sclerosis. J Neurosci Res 1994; 37: 169–181.
  • Bourdette DN, Whitham RH, Chou YK, et al. Immunity to TCR peptides in multiple sclerosis. I. Successful immunization of patients with synthetic V beta 5.2 and V beta 6.1 CDR2 peptides [published erratum appears in J Immunol 1994 Jul 15;153 (2): 910]. J Immunol 1994; 152: 2510–2519.
  • Vandenbark AA, Chou YK, Whitham R, et al. Treatment of multiple sclerosis with T-cell receptor peptides: results of a double-blind pilot trial [see comments] [published erratum appears in Nat Med 1997; 3 (2): 240]. Nat Med 1996; 2: 1109-1115.
  • Hafler DA, Saadeh MG, Kuchroo VK, Milford E, Steinman L. TCR usage in human and experimental demyeli-nating disease. Immunol Today 1996; 17: 152–159.
  • Valli A, Sette A, Kappos L, et al. Binding of myelin basic protein peptides to human histocompatibility leukocyte antigen class II molecules and their recognition by T cells from multiple sclerosis patients. J Clin Invest 1993; 91: 616–628.
  • Ben-Nun A, Liblau RS, Cohen L, et al. Restricted T-cell receptor VI3 usage by myelin basic protein-specific T cell clones in multiple sclerosis: Predominant genes vary in individ-uals. Proc Natl Acad Sci USA 1991; 88: 2466-2470.
  • Springer TA. Traffic signals for lymphocyte recircula-tion and leukocyte emigration: the multistep paradigm. Cell 1994; 76: 301–314.
  • McMurray RW. Adhesion molecules in autoimmune disease. Semin Arthritis Rheum 1996; 25: 215–233.
  • Muraro PA, Leist T, Bielekova B, McFarland HF. VLA-4/CD49d downregulated on primed T lymphocytes dur-ing interferon-beta therapy in multiple sclerosis. J Neuroimmunol 2000; 111: 186–194.
  • Gonzalez-Amaro R, Diaz-Gonzalez F, Sanchez-Madrid F. Adhesion molecules in inflammatory diseases. Drugs 1998; 56: 977–988.
  • Baggiolini M. Chemokines and leukocyte traffic. Nature 1998; 392: 565–568.
  • Wells TN, Power CA, Proudfoot AE. Definition, func-tion and pathophysiological significance of chemokine recep-tors. Trends Pharmacol Sci 1998; 19: 376–380.
  • Sorensen TL, Tani M, Jensen J, et al. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 1999; 103: 807–815.
  • Huang D, Han Y, Rani MR, et al. Chemokines and chemokine receptors in inflammation of the nervous system: manifold roles and exquisite regulation. Immunol Rev 2000; 177: 52–67.
  • Ransohoff RM, Bacon KB. Chemokine receptor antag-onism as a new therapy for multiple sclerosis. Expert Opin Investig Drugs 2000; 9: 1079–1097.

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