Abstract
The understanding of the immunological processes involved in T cell-mediated disease in humans has greatly benefited from the study of similar processes in animals [11. Whether induced by a specific antigen or spontaneously occurring, all have lent insight to and sometimes confused the puzzle of the etiology and pathogenesis of human disease. This chapter emphasizes three major examples of organ-specific and systemic animal models of T cell-mediated disease in mice. Organ-specific diseases are either antigen-induced, as in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), transplant allograft rejection, or graft versus host disease (GVHD), or occur spontaneously as for models of insulin-dependent diabetes mellitus (IDDM). The primary animal model of systemic autoimmune disease is a spontaneously occurring syndrome in inbred mice which resembles human systemic lupus erythematosus (SLE). The goal is to provide a descriptive analysis of a few select models with regard to what is known of the etiology and pathogenesis and to afford opportunities for evaluation of new therapeutic targets and mechanisms for the treatment of human immunological disorders which are the result of T cell regulatory processes. Finally, since animal models are constructs either experimentally or from nature as prototypes of human disease, it should be noted that there are as many subtle differences as there are overt similarities. This should always be kept within the investigators’ hypotheses and interpretations.
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References
Rose NR (1989) Pathogenic mechanisms in autoimmune diseases. Clin Immunol Immunopathol 53 (Suppl): 57–516
Cohen IR (1992) The cognitive paradigm and the immunological homunculus. Immunol Today 13: 490–494
Bona C (1991) Postulates defining pathogenic autoantibodies and T cells. Autoimmunity 10: 169–172
Rose NR, Bona C (1993) Defining criteria for autoimmune diseases (Witebsky’s postulates revisited). Immunol Today 14: 426–430
Nepom G, Erlich H (1991) MHC class-II molecules and autoimmunity. Annu Rev Immunol 9: 493–525
Wicker LS (1997) Major Histocompatibility Complex-linked control of autoimmunity. J Exp Med 186: 973–975
Greenwald RA, Diamond HS (eds) (1988) CRC Handbook of animal models for the rheumatic diseases, Volume II. CRC Press, Boca Raton, 181–183
van Gelder M, Mulder AH, van Bekkum DV (1996) Treatment of relapsing experimental autoimmune encephalomyelitis with largely MHC-matched allogeneic bone marrow transplantation. Transplantation 62: 810–818
Cruse JM, Lewis RE (1988) Cellular interactions in autoimmunity. Concepts Immunopathol 6: 1–21
Rees AD, Lombardi G, Scoging A, Barber 1, Mitchell D, Lamb J, Lechler R (1989) Functional evidence for the recognition of endogenous peptides by autoreactive T cell clones. Int Immunol 1: 624–630
Fowell D, Mason D (1993) Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential. J Exp Med 177: 627–636
Saoudi A, Seddon B, Heath V, Fowell D, Mason D (1996) The physiological role of regulatory T cells in the prevention of autoimmunity: the function of the thymus in the generation of the regulatory T cell subset. Immunol Rev 149: 195–216
Zamvil S, Nelson P, Trotter J, Mitchell D, Knobler R, Fritz R, Steinman L (1985) T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317: 355–358
Serreze DV, Leiter EH, Worthen SM, Shultz LD (1988) NOD marrow stem cells adop- tively transfer diabetes to resistant (NOD x NOD)F1 mice. Diabetes 37: 252–255
Kotb M (1995) Infection and autoimmunity: A story of the host, the pathogen, and the copathogen. Clin Immunol Immunopathol 74: 10–22
Yoon JW (1991) Role of virus in the pathogenesis of IDDM. Ann Med 23: 437–445
Oldstone MB (1997) Viruses in autoimmune diseases. Scand J Immunol 46: 320–325
Sercarz EE, Lehmann PV, Ametani A, Benichou G, Miller A, Moudgil K (1993) Dominance and crypticity of T cell antigenic determinants. Annu Rev Immunol 11: 229–266
Owens T, Sriram S (1995) The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis. Neurol Clin 13: 51–73
Swarnborg RH (1995) Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease. Clin Immunol Immunopathol 77: 4–13
Bach JF (1994) Insulin-dependent diabetes mellitus as an autoimmune disease. Endocrine Rev 15: 516–542
Kroemer G, Martinez C (1991) Cytokines and autoimmune disease. Clin Immunol Immunopathol 61: 275–295
Feldman M, Brennan FM, Chanty D, Haworth C, Turner M, Katsikis P, Londer M, Abney E, Buchan G, Barrett K et al (1991) Cytokine assays: Role in evaluation of the pathogenesis of autoimmunity. Immunol Rev 119: 105–123
Mossman TR (1991) Cytokine secretion patterns and crossregulation of T cell subsets. Immunol Res 10: 183–188
van Bekkum DW (1994) Biology of acute and chronic graft-versus-host reactions: predictive value of studies in experimental animals. Bone Marrow Transpl 14 (Suppl 4): 51–55
Holoshitz J, Matitiau A, Cohen IR (1984) Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II. J Clin Invest 73: 211–215
Taurog J (1983) The cellular basis of adjuvant arthritis. II. Characterization of the cells mediating passive transfer. Cellular Immunol 80: 198–204
Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980) Breeding of a non-obese, diabetic strain of mice. Exp Anim 29: 1–13
Nakhooda AF, Like AA, Chappel CI, Murray FT, Marliss EB (1977) The spontaneous- ly diabetic Wistar rat. Metabolic and morphologic studies. Diabetes 26: 100–112
Leiter E (1998) The NOD mouse: A model for insulin-dependent diabetes. In: Shevach EM, Coico R (eds): Current protocols in immunology, Vol. 3. John Wiley & Sons, Inc, New York, Section 15. 9
Kikutani H, Makino S (1992) The murine autoimmune diabetes model: NOD and related strains. Adv Immunol 51: 285–322
Shieh D-C, Cornelius J, Winter W, Peck A (1993) Insulin dependent diabetes in the NOD mouse model. 1. Detection and characterization of autoantibody bound to the surface of pancreatic beta cells prior to development of the insulitis lesion in prediabetic NOD mice. Autoimmunity 15: 123–135
Bach JF (1995) Insulin-dependent diabetes mellitus as a beta-cell targeted disease of immunoregulation. J Autoimmunity 8: 439–463
Coleman DL (1980) Acetone metabolism in mice: increased activity in mice heterozygous for obesity genes. Proc Natl Acad Sci USA 77: 290–293
Wicker LS, Todd JA, Peterson LB (1995) Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol 13: 179–200
Ikegami H, Makino S, Yamato E, Kawaguchi Y, Ueda H, Sakamoto T, Takekawa K, Ogihara T (1995) Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping. J Clin Invest 96: 1936–1942
Lo D (1996) Transgenic and knockout models of autoimmunity: building a better disease? Clin Immunol Immunopathol 79: 96–104
Rossini AA, Handler ES, Mordes JP, Greiner DL (1995) Human autoimmune diabetes mellitus: Lessons from BB rats and NOD mice-Caveat Emptor. Clin Immunol Immunopathol 74: 2–9
Hutchings P, Rosent H, O’Reilly LA, Simpson E, Gordon S, Cooke A (1990) Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. Nature 348: 639–642
Wong S, Guerder S, Visintin I, Reich E-P, Swenson KE, Flavell RA, Janeway CA (1995) Expression of the co-stimulator molecule B7–1 in pancreatic beta-cells acclerates diabetes in the NOD mouse. Diabetes 44: 326–329
Katz JD, Benoist C, Mathis D (1995) T helper cell subsets in insulin-dependent diabetes. Science 268: 1185–1188
Serreze, DV, Hamaguchi K, Leiter EH (1993) Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmunity 2: 759–776
Fox CJ, Danska JS (1997) IL-4 expression at the onset of islet inflammation predicts nondestructive insulitis in nonobese diabetic mice. J Immunol 158: 2414–2424
Mueller R, Bradley LM, Krahl T, Sarvetnick N (1997) Mechanism underlying counter-regulation of autoimmune diabetes by IL-4. Immunity 7: 411–418
von Herrath MG, Oldstone MBA (1997) Interferon-y is essential for destruction of ß cells and development of insulin-dependent diabetes mellitus. J Exp Med 185: 531–539
Grewal IS, Grewal KD, Wong FS, Picarella DE, Janeway CA, Flavell RA (1996) Local expression of transgene encoded TNFŒ in islets prevents autoimmune diabetes in nonobese diabetic (NOD) mice by preventing the development of auto-reactive islet-specific T cells. J Exp Med 184: 1963–1974
McSorely SJ, Soldera S, Malherbe L, Carnaud C, Locksley RM, Flavell RA, Glaicherhaus N (1997) Immunological tolerance to a pancreatic antigen as a result of local expression of TNFct by islet ß cells. Immunology 7: 401–409
Serreze DV, Chapman HD, Varnum DS, Hanson MS, Reifsnyder PC, Richard SD, Fleming SA, Leiter EH, Shultz, LD (1997) B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Ig mu null mice. J Exp Med 184: 2049–2053
Dallas-Pedretti A, McDuffie M, Haskins K (1995) A diabetes-associated T-cell autoantigen maps to a telomeric locus on mouse chromosome 6. Proc Natl Acad Sci USA 92: 1386–1390
Martin R, McFarland HF (1995) Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis. Crit Rev Clin Lab Sci 32: 121–182
Hafler DA, Weiner HL (1995) Immunological mechanisms and therapy in multiple sclerosis. Immunol Rev 144: 75–107
Scolding NJ, Zajicek JP, Wood N, Compston DS (1994) The pathogenesis of demyelinating disease. Prog Neurobiol 43: 143–173
Sriram S, Carroll L, Fortin S, Cooper S, Ranges G (1988) In vitro immunomodulation by monoclonal anti-CD4 antibody: II. Effect on T cell response to myelin basic protein and experimental allergic encephalomyelitis. J Immunol 141: 464–468
Schmidt S, Linington C, Zipp F, Sotgiu S, de Waal Malefyt R, Wekerle H, Hohlfeld R (1997) Multiple sclerosis: comparison of the human T-cell response to S100 beta and myelin basic protein reveals parallels to rat experimental panencephalitis. Brain 120: 1437–1445
Barron JJ, Madri N, Ruddle G, Hashim G, Janeway CA (1993) Surface expression of a4-integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 177: 57–68
Renno T, Krakowski M, Piccirillo C, Lin J, Owens T (1995) TNFa expression by resident microglia and infiltrating leukocytes in the central nervous system of experimental allergic encephalomyelitis: regulation by TH1 cytokines. J Immunol 154: 944–953
Godiska R, Chantry D, Dietsch GN, Gray PW (1994) Chemokine expression in murine experimental allergic encephalomyelitis. J Neuroimmunol 58: 167–176
Karpus WJ, Kennedy KJ (1997) MIP-1a and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as TH1/TH2 lymphocyte differentiation. J Leuk Biol 62: 681–687
Gladue RP, Carroll L, Milici AJ, Pettipher ER, Salter ED, Contillo L, Showell H (1996) Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis. J Exp Med 183: 1893–1898
Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, Dalton D, Fathman CG (1996) Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 156: 5–7
Rose LM, Richards TL, Peterson J, Petersen R, Alvord EC (1997) Resolution of CNS lesions following treatment of experimental allergic encephalomyelitis in macaques with monoclonal antibody to the CD18 leukocyte antigen. Multiple Sclerosis 2: 259–266
Goverman J, Woods A, Larson L, Weiner LP, Hood L, Zaller DM (1993) Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72: 551–560
Wang LY, Fujinami RS (1997) Enhancement of EAE and induction of autoantibodies to T-cell epitopes in mice infected with a recombinant vaccinia virus encoding myelin proteolipid protein. J Neuroimmunol 75: 75–83
Ichikawa M, Johns TG, Adelmann M, Bernard CC (1996) Antibody response in Lewis rats injected with myelin oligodendrocyte glycoprotein derived peptides. Int Immunol 8: 1667–1674
Hartung HP, Rieckmann P (1997) Pathogenesis of immune-mediated demyelination in the CNS. J Neural Transmission 50: 173–181
Devaux B, Enderlin F, Wallner B, Smilek DE (1997) Induction of EAE in mice with recombinant human MOG and treatment of EAE with a MOG peptide. J Neuroimmunol 75: 169–173
Kerlero de Rosbo N, Mendel I, Ben-Nun A (1995) Chronic relapsing experimental autoimmune encephalomyelitis with a delayed onset and an atypical clinical course induced in PL/J mice by myelin oligodendrocyte glycoprotein (MOG)-derived peptide: preliminary analysis of MOG T cell epitopes. Eur J Immunol 25: 985–993
Ding M, Wong JL, Rogers NE, Ignarro LJ, Voskuhl RR (1997) Gender differences in inducible nitric oxide production in SJL/J mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 77: 99–106
Berger T, Weerth S, Kojima K, Wekerle H, Lassmann H (1997) Experimental autoimmune encephalmyelitis: the antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system. Lab Invest 76: 355–364
Bernard CC, Johns TG, Slavin A, Ichikawa M, Ewing C, Liu J, Bettadapura J (1997). Myelin oligodendrocyte glycoprotein: a novel candidate autoantigen in multiple sclerosis. J Mol Med 75: 77–88
Lafaille JJ, Keere FV, Hsu AL, Baron JL, Haas W, Raine CS, Tonegawa S (1997) Myelin basic protein specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease. J Exp Med 186: 307–312
Cannella B, Gao YL, Brosnam C, Raine CS (1996) IL-10 fails to abrogate experimental autoimmune encephalomyelitis. J Neuroscience Res 45: 735–746
Shaw MK, Lorens JB, Dhawan A, DalCanto R, Tse HY, Tran AB, Bonpane C, Eswaran C, Eswaran SL, Brocke S, Sarvetnick N, Steinman L, Nolan GP, Fathman CG (1997) Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis. J Exp Med 185: 1711–1714
Liblau R, Steinman L, Brocke S (1997) Experimental autoimmune encephalomyelitis in IL-4 deficient mice. Int Immunol 9: 799–803
Conboy IM, DeKruyff RH, Tate KM, Cao ZA, Moore TA, Umetsu DT, Jones PP (1997) Novel genetic regulation of T helper 1 (Th1/Th2) cytokine production and encephalogenecity in inbred mouse strains. J Exp Med 185: 439–451
Smith T, Hewson AK, Kingsley CL, Leonard JP, Cuzner ML (1997) Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat. Am J Pathol 150: 1909–1917
Segal BM, Stevach EM (1996) IL-12 unmasks latent autoimmune disease in resistant mice. J Exp Med 184: 771–775
Gladue RP, Laquerre AM, Magna HA, Carroll LA, O’Donnell M, Changelian PS, Franke AE (1994) In vivo augmentation of IFNy with a rIL-12 human /mouse chimera: pleiotropic effects against infectious agents in mice and rats. Cytokine 6: 318–328
Leonard JP, Waldburger KE, Goldman SJ (1996) Regulation of experimental autoimmune encephalomyelitis by interleukin-12. Ann NY Acad Sci 795: 216–226
Korner H, Lemckert FA, Chaudhri G, Etteldorf S, Sedgwick JD (1997) Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system. Eur J Immunol 27: 1973–1981
Taupin V, Renno T, Bourbonniere L, Peterson A., Rodriguez M, Owens T (1997) Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system. Eur J Immunol 27: 905–913
Sun D, Hu X, Liu X, Whitaker JN, Walker WS (1997) Expression of chemokine genes in rat glial cells: the effect of myelin basic protein reactive encephalogenic T cells. J Neurosci Res 48: 192–200
Miyagishi R, Kikuchi S, Takayama C, Inoue Y, Tashiro K (1997) Identification of cell types producing RANTES, MIP-1 alpha, and MIP-1 beta in rat experimental autoimmune encephalomyelitis by in situ hybridization. J Neuroimmunol 77: 17–26
Rollins BJ (1997) Chemokines. Blood 90: 909–928
Sabelko KA, Kelly KA, Nahm MH, Cross AH, Russell JH (1997) Fas and Fas ligand enhance the pathogenesis of experimental allergic encephalomyelitis, but are not essential for immune privilege in the central nervous system. J Immunol 159: 3096–3099
Waldner H, Sobel RA, Howard E, Kuchroo VK (1997) Fas-and FasL-deficient mice are resistant to induction of autoimmune encephalmyelitis. J Immunol 159: 3100–3103
Clements JM, Cossins JA, Wells GM, Corkill DJ, Helfrich K, Wood LM, Pigott R, Stabler G, Ward GA, Gearing AJ, Miller KM (1997) Matrix metalloproteinase expression during experimental autoimmune encephalmyelitis and effects of a combined matrix metalloproteinase and tumor necrosis factor-alpha inhibitor. J Neuroimmunol 74: 8594
Stinissen P, Raus J, Zhang J (1997) Autoimmune pathogenesis of multiple sclerosis: role of autoreactive T lymphocytes and new immunotherapeutic strategies. Crit Rev Immunol 17: 33–75
Poliak S, Mor F, Conlon P, Wong T, Ling N, Rivier J, Vale W, Steinman L (1997) Stress and autoimmunity: the neuropeptides corticotropin-releasing factor and urocortin suppress encephalomyelitis via effects on both the hypothalmic-pituitary adrenal axis and the immune system. J Immunol 158: 5751–5756
Bolton C, O’Neill JK, Allen SJ, Baker D (1997) Regulation of chronic relapsing experimental allergic encephalomyelitis by endogenous and exogenous glucocorticoids. Int Archives Allergy Imm 114: 74–80
Kobayashi Y, Kawai K, Ito K, Honda H, Sobue G, Yoshikai Y (1997) Aggravation of murine experimental allergic encephalomyelitis by administration of T-cell receptor gamma-delta-specific antibody. J Neuroimmunol 73: 169–174
Martin R, McFarland H (1996) Experimental immunotherapies for multiple sclerosis. Sem Immunopathol 18: 1–24
Gerritse K, Deen C, Fasbender M, Ravid R, Boersma W, Claassen E (1994) The involvement of specific anti-myelin basic protein antibody-forming cells in multiple sclerosis immunopathology. J Neuroimmunol 49: 153–159
Merelli E, Bedin R, Sola P, Barozzi P, Mancardi GL, Ficarra G, Franchini G (1997) Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults, and children. J Neurology 244: 450–454
Yu M, Nishiyama A, Trapp BD, Tuohy VK (1996) Interferon-beta inhibits progression of relapsing-remitting experimental autoimmune encephalomyelitis. J Neuroimmunol 64: 91–100
Brod SA, Nelson LD, Khan M, Wolinsky JS (1997) IFN-beta 1ß treatment of relapsing multiple sclerosis has no effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion ex vivo after nine months. International J Neuroscience 90: 135–144
Weiner HL, Friedman A, Miller A, Khoury SJ, al-Sabbagh A, Santos L, Sayeh M, Nussenblatt RB, Trentham DE, Hafler DA (1994) Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Ann Rev Immunol 12: 809–837
Drake CG, Rozzo SJ, Vyse TJ, Palmer E, Kotzin BL (1995) Genetic contributions to lupus-like disease in (NZB x NZW)F1 mice. Immunol Rev 144: 51–74
Kotzin BL (1997) Susceptibility loci for lupus: A guiding light from murine models. J Clin Invest 99: 557–558
Steinberg AD, Huston DP, Taurog JD, Cowdery JS, Raveche ES (1981) The cellular and genetic basis of murine lupus. Immunol Rev 55: 121–154
Peng SL, Craft J (1996) T cells in murine lupus: propagation and regulation of disease. Molec Biol Rep 23: 247–251
Vyse TJ, Kotzin BL (1996) Genetic basis of systemic lupus erythematosus. Cur Opin Immunol 8: 843–851
Corna D, Morigi M, Facchinetti D, Bertani T, Zoja C, Remuzzi G (1997) Mycophenolate mofetil limits renal damage and prolongs life in murine lupus autoimmune disease. Kid Internat 51: 1583–1589
Serreze DV, Leiter EH (1994) Genetic and pathogenic basis of autoimmune diabetes in NOD mice. Cur Opin Immunol 6: 900–906
Mueller R, Sarvetnick N (1995) Transgenic/knockout mice-tools to study autoimmunity. Cur Opin Immunol 7: 799–803
Renold AE, Porte D, Shafrir E (1988) In: E Shafrir, AE Renold (eds): Frontiers in diabetes research: Lessons from animal diabetes II. Libbey, London, 3–5
Allison AC, Lafferty KJ, Fliri H (eds) (1993) Immunosuppressive and antiinflammatory drugs. Annals of New York Academy of Sciences, vol 696
St. Georgiev V, Yamaguchi H (eds) (1993) Immunomodulating drugs. Annals of New York Academy of Sciences, vol 685
Przepiorka D, Sollinger H (eds) (1995) Recent developments in transplantation medicine. Volume I. New immunosuppressive drugs. Physician and Scientist Publishing Co., Inc., Illinois
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Weringer, E.J., Gladue, R.P. (1999). T cell-mediated diseases of immunity. In: Morgan, D.W., Marshall, L.A. (eds) In Vivo Models of Inflammation. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7775-6_10
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