Experimental models of relapsing-remitting multiple sclerosis: Current concepts and perspective

Current Neurovascular Research

Volumn 2, Issue 4, 2005, Pages 349-362

  Skundric, Dusanka S ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autoimmune encephalomyelitis; Demyelination; Experimental models; Multiple sclerosis; Neurodegeneration; Neuroinflammation; Relapsing remitting MS

Indexed keywords

ANTIBODY; MYELIN;

ALLERGIC ENCEPHALOMYELITIS; AUTOIMMUNE DISEASE; CENTRAL NERVOUS SYSTEM; DEMYELINATION; DISEASE COURSE; EXPERIMENTAL MODEL; HUMAN; INFLAMMATION; MULTIPLE SCLEROSIS; NERVE CELL LESION; NERVE FIBER DEGENERATION; NONHUMAN; OLIGODENDROGLIA; PRIORITY JOURNAL; RELAPSE; REMISSION; REVIEW; T LYMPHOCYTE;

ANIMALS; AXONS; CENTRAL NERVOUS SYSTEM; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; GLIOSIS; HUMANS; INFLAMMATION; MODELS, NEUROLOGICAL; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; NERVE DEGENERATION;

EID: 24744470740     PISSN: 15672026     EISSN: None     Source Type: Journal    
DOI: 10.2174/156720205774322601     Document Type: Review

References (99)

1. Abdul-Majid KB, Jirholt J, Stadelmann C, Stefferl A, Kjellen P, Wallstrom E, Hojmdahl R, Lassmann H, Oison T, Harris RA. (2000) Screening of several H-2 congenic mouse strains identified H-2q mice as highly susceptible to MOG-induced EAE with minimal adjuvant requirement. J Neuroimmunol 111: 23-33.
2. Adelmann M, Wood J, Benzel I, Fiori P, Lassmann H, Matthieu JM, Gardinier MV, Dornmair k, Linington C. (1995) The N-therminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. J Neuroimmunol 63: 17-27.
3. Alters SE, Sakai K, Steinman L, Oi VT. (1990) Mechanisms of anti-CD4-mediated depletion and immunotherapy. A study using a set of chimeric anti-CD4 antibodies. J Immunol 144: 4587-92.
4. Amor S, Groome N, Linington C, Morris MM, Dornmair K, Gardinier MV, Matthieu JM, Baker D. (1994) Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. J Immunol 153: 4349-4356.
5. Amor S, O'Neill JK, Morris MM, Smith RM, Wraith DC, Groome N, Travers PJ, Baker D. (1996) Encephalitogenic epitopes of myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein for experimental allergic encephalomyelitis induction in Biozzi ABH (H-2Ag7) mice share an amino acid motif. J Immunol 156: 3000-8.
6. Barnett MH, Prineas JW. (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 55: 458-468.
7. Benoist C, Mathis D. (2001) Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? Nat Immunol 2: 797-801.
8. Benveniste EN, Benos DJ. (1995) TNF-a- and INF-y-mediated signal transduction pathways: effects on flial cell gene expression and function. FASEB J 9: 1577-1584.
9. Berman JW, Guida MP, Warren J, Amat J, Brosnan CF. (1996) Localization of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat. J Immunol 156: 3017-23.
10. Biasi G, Facchinetti A, Monastra G, Mezzalira S, Sivieri S, Tavolato B, Gallo P. (1997) Protection from experimental autoimmune encephalomyelitis (EAE): non-depleting anti-CD4 mAb treatment induces peripheral T-cell tolerance to MBP in PL/J mice. J Neuroimmunol 73: 117-23.
11. Biddison WE, Cruikshank WW, Center DM, Pelfrey CM, Taub DD, Turner RV (1998) CD8+ myelin-peptide specific T cells can chemoattract CD4+ myelin-peptide specific T cells: importance of IFN-inducible protein 10. J Immunol 160: 444-448.
12. Bjartmar C, Trapp BD. (2003) Axonal degeneration and progressive neurologic disability in multiple sclerosis. Neurotox Res 5: 157-64.
13. Bruk HP, Uccelli A, Kerlero De Rosbo N, Bontrop RE, Roccatagliate L, de Groot NG, Capelio E, Laman JD, Ben-Nun A, Hart BA. (2000) Myelin/oligodendrocyte glycoprotein induced autoimmune encephalomyelitis in common marmosets: the encephalitogenic T cell epitope pMOG24-36 is presented by a monomorphic MHC class II molecule. J Immunol 165: 1093-2010.
14. Bromley SK, Peterson DA, Gunn MD, Dustin ML. (2000) Cutting edge: hierarchy of chemokine receptor and TCR signals regulating T cell migration and proliferation. J Immunol 165: 15-9.
15. Brown A, McFarlin DE, Raine CS. (1982) Chronologic neuropathology of relapsing experimental allergic encephalomyelitis in the mouse. Lab Invest 46: 171-85.
16. Chataway J, Feakes R, Coraddu F, Gray J, Deans J, Fraser M, Robertson N, Broadley S, Jones H, Clayton D, Goodfellow P, Sawcer S, Compston A. (1998) The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen. Brain 121: 1869-87.
17. Chitnis T, Khoury SJ. (2003) Cytokine shifts and tolerance in experimental autoimmune encephalomyelitis. Immunol Res 28: 223-239.
18. Colover J. (1980) A new pattern of spinal-cord demyelination in guinea pigs with acute experimental allergic encephalomyelitis mimicking multiple sclerosis. Br J Exp Pathol: 390-400.
19. Croxford JL, Miller SD. (2003) Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212. J Clin Invest 111: 1231-1240.
20. Cruikshank WW, Kornfeld H, Center DM. (2000) Interleukin-16. J Leukoc Biol 67:757-66.
21. Dooms H, Abbas AK. (2002) Life and Death in effector T cells. Nat Immunol 3: 797-798.
22. Facchinetti A, Gallo P, Perini P, Mezzalira S, Ronchese F, Biasi G. (2004) The MBP-reactive repertoire is shaped by recognition of minor histocompatibility antigens. J Neuroimmunol 148: 154-161.
23. Fazekas G, Tabira T. (2000) What transgenic and knockout mouse models teach us about experimental autoimmune encephalomyelitis. Rev Immunogenet 2: 115-132.
24. Fife BT, Huffnagle GB, Kuziel WA, Karpus, WJ. (2000) CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 192: 899-905.
25. Furlan R, Poliani PL, Marconi PC, Bergami A, Ruffini F, Adorini L, Glorioso JC, Comi G, Martino G. (2001) Central nervous system gene therapy with interleukin-4 inhibits progression of ongoing relapsing-remitting autoimmune encephalomyelitis in Biozzi AB/H mice. Gene Therapy 8: 13-19.
26. Furtado GC, Olivares-Villagomez D, Curotto de Lafaille MA, Wensky AK, Latkowski JA, Lafaille JJ. (2001) Regulatory T cells in spontaneous autoimmune encephalomyelitis. Immunol Rev 182: 122-34.
27. Genain CP, Hauser SL. (2001) Experimental allergic encephalomyelitis in the new world monkey Callithrix jacchus. Immunol Rev 183: 159-72.
28. Glabinski AR, Tani M, Tuohy VK, Tuthill RJ, Ransohoff RM. (1995) Central nervous system chemokine mRNA accumulation follows initial leukocyte entry at the onset of acute murine experimental autoimmune encephalomyelitis. Brain Behav Immun 9: 315-30.
29. Glabinski AR, Tani M, Strieter RM, Tuohy VK, Ransohoff RM. (1997) Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis. Am J Pathol 150: 617-30.
30. Gu L, Rutledge B, Fiorillo J, Ernst C, Grewal I, Flavell R, Gladue R, Rollins B. (1997) In vivo properties of monocyte chemoattractant protein-1. J Leukoc Biol 62: 577-80.
31. Hafler DA, Saadeh MG, Kuchroo VK, Milford E, Steinman L. (1996) TCR usage in human and experimental demyelinating disease. Immunol Today 17: 152-159.
32. Haines JL, Bradford Y, Garcia ME, Reed AD, Neumeister E, Pericak-Vance MA, Rimmler JB, Menold MM, Martin ER, Oksenberg JR, Barcellos LF, Lincoln R, Hauser SL; Multiple Sclerosis Genetics Group (2002) Multiple susceptibility loci for multiple sclerosis. Hum Mol Genet 11: 2251-6.
33. Hayashi M, Luo Y, Laning J, Strieter RM, Dorf M, (1995) Production and function of monocytes chemoattractant protein-1 and other β-chemokines in murine glial cells. J Neuroimmunol 60: 143-150.
34. Hickey WF. (2001) Basic principles of immunological surveillance of the normal central nervous system. Glia 36: 118-124.
35. Hohlfeld R, Wekerle H. (2001) Immunological update on multiple sclerosis. Curr Opin Neurol 14: 299-304.
36. Holz A, Bielekova B, Martin R, Oldstone MB. (2000) Myelin-associated oligodendrocytic basic protein: identification of an encephalitogenic epitope and association with multiple sclerosis. J Immunol 164: 1103-1109.
37. Huang D, Han Y, Rani MR, Glabinski A, Trebst C, Sorensen T, Tani M, Wang J, Chien P, O'Bryan S, Bielecki B, Zhou ZL, Majumder S, Ransohoff RM. (2000) Chemokines and chemokine receptors in inflammation of the nervous system: manifold roles and exquisite regulation. Immunol Rev 177: 52-67.
38. Huang D, Wang J, Kivisakk P, Rollins BJ, Ransohoff RM. (2001) Absence of monocytes chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med 193: 713-725.
39. Iglesias A, Bauer J, Litzenburger T, Schubart A, Linington C. (2001) T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36: 220-234.
40. Imada K, Leonard WJ. (2000) The Jak-STAT pathway. Mol Immunol 37: 1-11.
41. Ivanoff J, Ivanoff A, Sundqvist KG. (2000) Defective chemokine production in T-leukemia cell lines and its possible functional role. Dev Immunol 7: 67-75.
42. Izikson L, Klein RS, Charo IE, Weiner HL, Luster AD. (2000) Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)Z. J Exp Med 192: 1075-1080.
43. Karpus WJ, Kennedy JK. (1997) MIP-1alpha and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as ThIAThZ lymphocyte differentiation. J Leukoc Biol 62: 681-7.
44. Kappos L, Comi G, Panitch H, Oger J, Antel J, et al., and the APL in Relapsing MS Study Group (2000) Induction of a non-encephalitogenic Th2 autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. Nat Med 6: 1176-82.
45. Kaser A, Dunzendorfer S, Offner FA, Ludwiczek O, Enrich B, Koch RO, Cruikshank WW, Wiedermann CJ, Tilg H. (2000) B lymphocyte-derived IL-16 attracts dendritic cells and Th Cells. J Immunol 165: 2474-2480.
46. 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.
47. Kerlero de Rosbo N, Hoffman M, Mendel I, Yust I, Kaye J, Bakimer R, Flechter S, Abramsky O, Milo R., Kami A, Ben-Nun A. (1997) Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions. Eur J Immunol 27: 3059-69.
48. Kerlero de Rosbo N, Brink HPM, Bauer J, Kaye JP, t'Hart BA, ben-Nun A. (2000) Rhesus monkeys are highly susceptible to experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte protein: characterization of immunodominant T and B cell epitopes. J Neuroimmunol 110: 83-96.
49. Khare M, Rodriguez M, David CS. (2003) HLA class II transgenic mice authenticate restriction of myelin oligodendrocyte glycoprotein-specific immune response implicated in multiple sclerosis pathogenesis. Int Immunol 4: 535-46.
50. Kuchroo VK, Anderson AC, Waldner H, Munder M, Bettelli E, Nicholson LB. (2002) T cell response in experimental autoimmune encephalo-myelitis (EAE): role of self and cross-reacitve antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire. Ann Rev Immunol 20: 101-23.
51. Lafaille JJ. (2004) T-cell receptor transgenic mice in the study of autoimmune diseases. J Autoimmun 22: 95-106.
52. Lassmann H, Bruck W, Lucchinetti C. (2001) Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 1: 115-21.
53. Lassmann H, Ransohoff RM. (2004) The CD4-Thl model for multiple sclerosis: a crucial re-appraisal. Trends Immunol 25: 132-137.
54. Lee SJ, Benveniste EN. (1999) Adhesion molecule expression and regulation on cells of the central nervous system. J Neuroimmunol 98: 77-88.
55. Lehmann D, Ben-Nun A. (1992) Intraperitoneal injection of CD4+ T cells induces CD5 B cells: Implications for a regulatory role of CD5 B cells in experimental autoimmune encephalomyelitis. Ann N Y Acad Sci 651: 579-80.
56. Lehmann PV, Forsthuber T, Miller A, Sercarz EE. (1992) Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 358: 155-7.
57. Lindert RB, Haase CG, Brehm U, Wekerle H, Linington C, Hohlfeld R. (1999) Multiple sclerosis: B and T cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein (MOG). Brain 122: 2089-2099.
58. Luther SA, Cyster JG. (2001) Chemokines as regulators of T cell differentiation. Nat Immunol 2: 102-7.
59. Lutton JD, Winston R, Rodman TC. (2004) Multiple Sclerosis: etiological mechanisms and future directions. Exp Biol Med 229: 12-20.
60. Madsen LS, Andersson EC, Jansson L, Krogsgaard M, Andersen CB, Engberg J, Strominger JL, Svejgaard A, Hjorth JP, Holmdahl R, Wucherpfennig KW, Fugger L. (1999) A humanized model for multiple sclerosis using HLA_DR2 and a human T-cell receptor. Nat Genet 23: 258-9.
61. Mars LT, Novak J, Liblau RS, Lehuen A. (2004) Therapeutic manipulation of iNKT cells in autoimmunity: modes of action and potential risks. Trends Immunol 25: 471-476.
62. Mokhtarian F, McFarlin DE, Raine CS. (1984) Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice. Nature 309: 356-8.
63. Nikolich-Zugich J, Slifka MK, Messaoudi I. (2004) The many important facets of T-cell repertoire diversity. Nat Rev Immunol 2: 123-32.
64. Olson JK, Ludovic M, Croxford J, Miller SD. (2004) Innate and adaptive immune requirements for induction of autoimmune demyelinating disease by molecular mimicry. Mol Immunol 40: 1103-1108.
65. Olson T, Dahlman E, Wallstrom E, Weissert R, Piehl F. (2000) Genetics of rat neuroinflammation. J Neuroimmuno 107:191-200.
66. Papenfuss TL, Rogers CJ, Gienapp I, Yurrita M, McClain M, Damico N, Valo J, Song F, Whitacre CC. (2004). Sex differences in experimental autoimmune encephalomyelitis in multiple murine strains. J Neuroimmunol 150: 59-69.
67. Pedotti R, De Voss JJ, Steinman L, Galli SJ. (2003). Involvement of both "allergic" and "autoimmune" mechanisms in EAE, MS and other autoimmune diseases. Trends in Immuno 24: 479-84.
68. Perera LP, Goldman CK, Waldmann TA. (1999). IL-15 induces the expression of chemokines and their receptors in T lymphocytes. J Immunol 162: 2606-12.
69. Prat A, Biernackl K, Wosik K, Antel JP. (2001) Glial cell influence on the human blood-brain barrier. Glia 36: 145-155.
70. Pribyl TM, Campagnoni CW, Kampf K, Kashima T, Handley VW, McMahon J, Campagnoni AT. (1993) The human myelin basic protein gene is included whtin a 179-kilobase transcription unit: expression in the immune and central nervous systems. Proc Natl Acad Sci USA 90: 10695-9.
71. Reddy J, Illes Z, Zhang X, Encinas J, Pyrdol J, Nicholson L, Sobel RA, Wucherpfennig KW, Kuchroo VK. (2004). Myelin proteolipid protein-specific CD4+CD25+regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 101:15434-9.
72. Ransohoff RM, Hamilton TA, Tani M, Stoler MH, Shick HE, Major JA, Estes ML, Thomas DM, Touhy VK. (1993) Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. FASEB J 7: 592-600.
73. Simpson J, Rezaie P, Newcombe J, Cuzner ML, Male D, Woodroofe MN. (2000). Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. J Neuroimmunol 108: 192-200.
74. Slavin A, Ewing C, Liu J, Ichikawa M, Slavin J, Bernard CC. (1998) Induction a multiple sclerosis-like disease in mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein. Autoimmunity 28, 109-20.
75. Smeltz RB, Wolf NA, Swanborg, RH. (1999) Inhibition of autoimmune T cell responses in the DA rat by bone marrow-derived NK cells in vitro: implications for autoimmunity. J Immunol 163: 1390-7.
76. Skundric DS, Huston K, Shaw M, Tse H, Raine CS. (1994) Experimental allergic encephalomyelitis: T cell trafficking to the central nervous system in a resistant Thy-1 congenic mouse strain. Lab Invest 71: 671-679.
77. b/s mice. J Neuroimmunol 136: 34-45.
78. Skundric DA, Dai R, Zakarian VL, Bessert D, Skoff RP, Cruikshank WW, Kurjakovic Z. (2005) Anti-IL-16 therapy reduces CD4+ T cell infliltration and improves paralysis and histopathology of relapsing EAE J Neurosci Res 79: 680-693.
79. Starr TK, Jameson SC, Hogquist KA. (2003) Positive and negative selection ofT cells. Ann Rev Immunol 21: 139-176.
80. Stefferl A, Brehm U, Storch M, Lambracht-Washington D, Bourquin C, Wonigeit K, Lassmann H, Linington C. (1999) Myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis in the resistant Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on B cell response. J Immunol 163: 40-47.
81. Steinman L. (2001) Multiple sclerosis: a two-stage disease. Nat Immunol 2: 762-764.
82. Steinman L, Roland M, Bernard C, Conlon P, Oksenberg JR. (2002) Multiple sclerosis: Deeper understanding of its pathogenesis reveals new targets for therapy. Ann Rev Neurosci 25: 491-505.
83. Steinman L. (2004) Immune therapy for autoimmune diseases. Science 305: 212-216.
84. Sun AD, Hu X, Liu X, Whitaker JN, Walker WS. (1997) Expression of chemokine genes in rat glial cells: the effect of myelin basic protein-reactive encephalitogenic T cells. J Neurosci Res 48: 192-200.
85. Sun D, Wekerle H. (1986) 1a-restricted encephalitogenic T lymphocytes mediating EAE lyse autoantigen-presenting astrocytes. Nature 320: 70-2.
86. Sun D, Whitaker JN, Huang Z, Liu D, Coleclough C, Wekerle H, Raine CS. (2001) Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice. J Immunol 166: 7579-87.
87. Taub DD, Ortaldo JR, Turcovski-Corrales SM, Key ML, Longo DL, Murphy WJ. (1996) Beta chemokines costimulate lymphocyte cytolysis, proliferation, and lymphokine production. J Leukoc Biol 59: 81-9.
88. Teuscher C, Butterfield RJ, Ma RZ, Zachary JF, Doerge RW, Blankenhorn EP. (1999) Sequence polymorphisms in the chemokines Scyal (TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scyal2 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic encephalomyelitis. J Immunol 163: 2262-6.
89. Theien BE, Vanderlugt CL, Nickerson-Nutter C, Cornebise M, Scott DM, Perper SJ, Whalley ET, Miller SD. (2003) Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE. Blood 102: 4464-4471.
90. Trebst C, Ransohoff RM. (2001) Investigating chemkokines and chemokine receptors in patients with multiple sclerosis. Arch Neurol 58: 1975-80.
91. Tsunoda I, Kuang LQ, Theil DJ, Fujinami RS. (2000) Antibody association with a novel model for primary progressive multiple sclerosis: induction of relapsing-remitting and progressive forms of EAE in H-2s mouse strains. Brain Pathol 10: 402-418.
92. Vanderlugt CL, Begolka WS, Neville KL, Katz-Levy Y, Howard LM, Eagar TN, Bluestone JA, Miller SD. (1998) The functional significance of epitope spreading and its regulation by co-stimulatory molecules. Immunol Rev 164: 63-72.
93. Voskuhl RR, Pribyl TM, Kampf K, Handley V, Liu HB, Feng J, Campagnoni CW, Soldan SS, Messing A, Campagnoni AT. (2003) Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous golli MBP knockout mice. J Nuroimmunol 139: 44-50.
94. Weiner LP, Louie KA, Atalla LR, Kochounian HH, Du J, Wei W, Hinton DR, Gordon EM, Anderson WF, McMillan M. (2004) Gene therapy in a murine model for clinical application to multiple sclerosis. Ann Neurol 55: 390-399.
95. Wucherpfennig KW, Catz I, Hausmann S, Strominger JL, Steinman L, Warren KG. (1997) Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted Tcell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes. J Clin Invest 100: 111-22.
96. Zamvil SS, Steinman L. (2003) Diverse targets for intervention during inflammatory and neurodegenerative phases of Multiple Sclerosis. Neuron 38: 685-688.
97. Zhang, T. Yamamura, T. Kondo, M. Fujiwara, and T. Tabira. (1997) Regulation of experimental autoimmune encephalomyelitis by natural killer cells. J Exp Med 186: 1677-87.
98. Zhang GX, Yu S, Gram B, Li J, Calida D, Ventura E, Chen X, Rostami A. (2004) T cell and antibody responses in remitting-relapsing experimental autoimmune encephalomyelitis in (C57BL/6 x SJL) F1 mice. J Neuroimmunol 148: 1-10.
99. Zlokovic BV, Skundric DS, Segal MB, Lipovac MN, Mackic JB, Davson H. (1990) A saturable mechanism for transport of immunoglobulin G across the blood-brain barrier of the guinea pig. Exp Neurol 107: 263-270.