Current trends in multiple sclerosis research: An update on pathogenic concepts

Acta Neurologica Belgica

Volumn 106, Issue 4, 2006, Pages 180-190

  Vanderlocht, Joris ^a   Hellings, Niels ^a   Hendriks, Jerome J A ^a   Stinissen, Piet ^a  

^a HASSELT UNIVERSITY   (Belgium)

Author keywords

Axonal injury; CD8 T cells; Multiple sclerosis; Pathogenic heterogeneity

Indexed keywords

ALEMTUZUMAB; BETA INTERFERON; BETA1A INTERFERON; BETASEON; DACLIZUMAB; GELATINASE A; GELATINASE B; GLATIRAMER; GLUCOCORTICOID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERFERON BETA SERINE; INTERLEUKIN 10; METHYLPREDNISOLONE; MITOXANTRONE; NATALIZUMAB; NEUROTROPHIC FACTOR; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG;

ANTIGEN SPECIFICITY; APOPTOSIS; AXONAL INJURY; BLOOD BRAIN BARRIER; BRAIN INFECTION; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CLINICAL FEATURE; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; GENETIC PREDISPOSITION; GENETIC SUSCEPTIBILITY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNOTHERAPY; MAJOR HISTOCOMPATIBILITY COMPLEX; MULTIPLE SCLEROSIS; NEUROPATHOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; REVIEW; TISSUE INJURY; VACCINATION; VIRUS MENINGITIS;

EID: 33846995128     PISSN: 03009009     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (151)

1. Noseworthy J. H., Lucchinetti C., Rodriguez M., Weinshenker B. G. Multiple sclerosis. N. Engl. J. Med., 2000, 343 (13): 938-952.
2. Hickey W. F. The pathology of multiple sclerosis: a historical perspective. J. Neuroimmunol., 1999, 98 (1): 37-44.
3. Lassmann H., Bruck W., Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol. Med., 2001, 7 (3): 115-121.
4. McFarlin D. E., McFarland H. F. Multiple sclerosis (first of two parts). N. Engl. J. Med., 1982, 307 (19): 1183-1188.
5. Smith K. J., McDonald W. I. The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 1999, 354 (1390): 1649-1673.
6. Fazekas F., Barkhof F., Filippi M., Grossman R. I., Li D. K., McDonald W. I., McFarland H. F., Paty D. W., Simon J. H., Wolinsky J. S., Miller D.H. The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology, 1999, 53 (3): 448-456.
7. McDonald W. I., Compston A., Edan G., Goodkin D., Hartung H. P., Lublin F. D., McFarland H. F., Paty D. W., Polman C. H., Reingold S. C., Sandberg-Wollheim M., Sibley W., Thompson A., Van Den Noort S., Weinshenker B. Y., Wolinsky J. S. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Annals of Neurology, 2001, 50 (1): 121-127.
8. Thompson A. J., Polman C. H., Miller D. H., McDonald W. I., Brochet B., Filippi MM., X., De Sa J. Primary progressive multiple sclerosis. Brain, 1997, 120 (Pt 6): 1085-1096.
9. McFarland H. F. Correlation between MR and clinical findings of disease activity in multiple sclerosis. AJNR Am. J. Neuroradiol., 1999, 20 (10): 1777-1778.
10. Raine C. S., Scheinberg L. C. On the immunopathology of plaque development and repair in multiple sclerosis. J. Neuroimmunol., 1988, 20 (2-3): 189-201.
11. Lucchinetti C., Bruck W., Parisi J., Scheithauer B., Rodriguez M., Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol., 2000, 47 (6): 707-717.
12. Sospedra M., Martin R. Immunology of multiple sclerosis. Annu. Rev. Immunol., 2005, 23: 683-747.
13. Sadovnick A. D., Bulman D., Ebers G. C. Parent-child concordance in multiple sclerosis. Ann. Neurol., 1991, 29 (3): 252-255.
14. Ebers G. C., Koopman W. J., Hader W., Sadovnick A. D., Kremenchutzky M., Mandalfino P., Wingerchuk D. M., Baskerville J., Rice G. P. The natural history of multiple sclerosis: a geographically based study: 8: familial multiple sclerosis. Brain, 2000, 123 Pt 3: 641-649.
15. Ebers G. C., Bulman D. E., Sadovnick A. D., Paty D. W., Warren S., Hader W., Murray T. J., Seland T. P., Duquette P., Grey T. A population-based study of multiple sclerosis in twins. N. Engl. J. Med., 1986, 315 (26): 1638-1642.
16. Sadovnick A. D., Armstrong H., Rice G. P., Bulman D., Hashimoto L., Paty D. W., Hashimoto S. A., Warren S., Hader W., Murray T. J. A population-based study of multiple sclerosis in twins: update. Ann. Neurol., 1993, 33 (3): 281-285.
17. Ebers G. C., Sadovnick A. D., Risch N. J. A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature, 1995, 377 (6545): 150-151.
18. Sadovnick A. D., Ebers G. C., Dyment D. A., Risch N. J. Evidence for genetic basis of multiple sclerosis. The Canadian Collaborative Study Group. Lancet, 1996, 347(9017): 1728-1730.
19. Beck S., Cann H. M., Campbell R. D., Dunham I., Inoko H., Jazwinska E. C., Ragoussis J., Trowsdale J., Ziegler A. Third single chromosome 6 workshop: meeting report. DNA Seq., 1997, 8 (3): 113-129.
20. Fogdell A., Hillert J., Sachs C., Olerup O. The multiple sclerosis- and narcolepsy-associated HLA class II haplotype includes the DRB5*0101 allele. Tissue Antigens, 1995, 46 (4): 333-336.
21. Fogdell-Hahn A., Ligers A., Gronning M., Hillert J., Olerup O. Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. Tissue Antigens, 2000, 55 (2): 140-148.
22. Dyment D. A., Ebers G. C., Sadovnick A. D. Genetics of multiple sclerosis. Lancet Neurol., 2004, 3 (2): 104-110.
23. McFarland H. F. Twin studies and multiple sclerosis. Ann. Neurol., 1992, 32 (6): 722-723.
24. Kurtzke J. F. Epidemiologic evidence for multiple sclerosis as an infection. Clin. Microbiol. Rev., 1993, 6 (4): 382-427.
25. Dean G., Kurtzke J. F. On the risk of multiple sclerosis according to age at immigration to South Africa. Br. Med. J., 1971, 3 (777): 725-729.
26. Coo H., Aronson K. J. A systematic review of several potential non-genetic risk factors for multiple sclerosis. Neuroepidemiology, 2004, 23 (1-2): 1-12.
27. Johnson R. T. The virology of demyelinating diseases. Ann. Neurol., 1994, 36 Suppl: S54-S60.
28. Soldan S. S., Jacobson S. Role of viruses in etiology and pathogenesis of multiple sclerosis. Adv. Virus. Res., 2001, 56: 517-555.
29. Allen I., Brankin B. Pathogenesis of multiple sclerosis - the immune diathesis and the role of viruses. J. Neuropathol. Exp. Neurol., 1993, 52 (2): 95-105.
30. Miller S. D., Vanderlugt C. L., Begolka W. S., Pao W., Yauch R. L., Neville K. L., Katz-Levy Y., Carrizosa A., Kim B. S. Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading. Nat. Med., 1997, 3 (10): 1133-1136.
31. Stohlman S. A., Hinton D. R. Viral induced demyelination. Brain Pathol., 2001, 11 (1): 92-106.
32. Wucherpfennig K. W., Strominger J. L. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell, 1995, 80 (5): 695-705.
33. Sotgiu S., Pugliatti M., Fois M. L., Arru G., Sanna A., Sotghiu M. A., Rosati G. Genes, environment, and susceptibility to multiple sclerosis. Neurobiol. Dis., 2004, 17 (2): 131-143.
34. Kelly M. A., Cavan D. A., Penny M. A., Muovic C. H., Jenkins D., Morrissey S., Miller D. H., Barnett A. H., Francis D. A. The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome. Hum. Immunol., 1993, 37 (3): 185-191.
35. Ota K., Matsui M., Milford E. L., Mackin G. A., Weiner H. L., Hafler D. A. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature, 1990, 346 (6280): 183-187.
36. Zamvil S. S., Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol., 1990, 8: 579-621.
37. Martin R., McFarland H. F., McFarlin D. E. Immunological aspects of demyelinating diseases. Annu. Rev. Immunol., 1992,10: 153-187.
38. Zamvil S., Nelson P., Trotter J., Mitchell D., Knobler R., Fritz R., Seinman L. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature, 1985, 317 (6035): 355-358.
39. Zhang J., Markovic-Plese S., Lacet B., Raus J., Weiner H. L., Hafler D. A. Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J. Exp. Med., 1994, 179 (3): 973-984.
40. Oksenberg J. R., Panzara M. A., Begovich A. B., Mitchell D., Erlich H. A., Murray R. S., Shimonkevitz R., Sherritt M., Rothbard J., Bernard C. C. Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature, 1993, 362 (6415): 68-70.
41. Wucherpfennig K. W., Sette A., Southwood S., Oseroff C., Matsui M., Strominger J. L., Hafler D. A. Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J. Exp. Med., 1994, 179 (1): 279-290.
42. Chou Y. K., Vainiene M., Whitham R., Bourdette D., Chou C. H., Hashim G., Offner H., Vandenbark A. A. Response of human T lymphocyte lines to myelin basic protein: association of dominant epitopes with HLA class II restriction molecules. J. Neurosci. Res., 1989, 23 (2): 207-216.
43. Martin R., Howell M. D., Jaraquemada D., Flerlage M., Richert J., Brostoff S., Long E. O., McFarlin D. E., MCFarland H. F. A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis. J. Exp. Med., 1991, 173 (1): 19-24.
44. Fuller K. G., Olson J. K., Howard L. M., Croxford J. L., Miller S. D. Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease. Methods Mol. Med., 2004, 102: 339-361.
45. Fujinami R. S., Oldstone M. B. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science, 1985, 230 (4729): 1043-1045.
46. Croxford J. L., Olson J. K., Miller S. D. Epitope spreading and molecular mimicry as triggers of autoimmunity in the Theiler's virus-induced demyelinating disease model of multiple sclerosis. Autoimmun. Rev., 2002, 1 (5): 251-260.
47. Hemmer B., Jacobsen M., Sommer N. Degeneracy in T-cell antigen recognition - implications for the pathogenesis of autoimmune diseases. J. Neuro-immunol., 2000, 107 (2): 148-153.
48. Brocke S., Gaur A., Piercy C., Gautam A., Gijbels K., Fathman C. G., Steinman L. Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen. Nature, 1993, 365 (6447): 642-644.
49. Waldner H., Collins M., Kuchroo V. K. Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease. J. Clin. Invest., 2004, 113 (7): 990-997.
50. Segal B. M., Dwyer B. K., Shevach E. M. An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease. J. Exp. Med., 1998, 187 (4): 537-546.
51. Olson J. K., Croxford J. L., Miller S. D. Virus-induced autoimmunity: potential role of viruses in initiation, perpetuation, and progression of T-cell-mediated autoimmune disease. Viral Immunol., 2001, 14 (3): 227-250.
52. McMahon E. J., Bailey S. L., Castenada C. V., Waldner H., Miller S. D. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat. Med., 2005, 11 (3): 335-339.
53. Greter M., Heppner F. L., Lemos M. P., Odermatt B. M., Goebels N., Laufer T., Noelle R. J., Becher B. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat. Med., 2005, 11(3): 328-334.
54. Krakowski M. L., Owens T. Naive T lymphocytes traffic to inflamed central nervous system, but require antigen recognition for activation. Eur. J. Immunol., 2000, 30 (4): 1002-1009.
55. Cannella B., Cross A. H., Raine C. S. Adhesion-related molecules in the central nervous system. Upregulation correlates with inflammatory cell influx during relapsing experimental autoimmune encephalomyelitis. Lab. Invest., 1991, 65 (1): 23-31.
56. Hafler D. A., Weiner H. L. In vivo labeling of blood T cells: rapid traffic into cerebrospinal fluid in multiple sclerosis. Ann. Neurol., 1987, 22 (1): 89-93.
57. Steinman L., Martin R., Bernard C., Conlon P., Oksenberg J. R. Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy. Annu. Rev. Neurosci., 2002, 25: 491-505.
58. Persidsky Y. Model systems for studies of leukocyte migration across the blood - brain barrier. J. Neurovirol., 1999, 5 (6): 579-590.
59. Butcher E. C., Picker L. J. Lymphocyte homing and homeostasis. Science, 1996, 272 (5258): 60-66.
60. Hartung H. P., Aarchelos J. J., Zielasek J., Gold R., Koltzenburg M., Reiners K. H., Toyka K. V. Circulating adhesion molecules and inflammatory mediators in demyelination: a review. Neurology, 1995, 45 (6 Suppl. 6): S22-S32.
61. Cuzner M. L., Opdenakker G. Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system. J. Neuro-immunol., 1999, 94 (1-2): 1-14.
62. Yong V. W., Krekoski C. A., Forsyth P. A., Bell R., Edwards D. R. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci., 1998, 21 (2): 75-80.
63. Leppert D., Waubant E., Galardy R., Bunnett N. W., Hauser S. L. T cell gelatinases mediate basement membrane transmigration in vitro. J. Immunol., 1995, 154 (9): 4379-4389.
64. Fierz W., Endler B., Reske K., Wekerle H., Fontana A. Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation. J. Immunol., 1985, 134 (6): 3785-3793.
65. Carson M. J., Reilly C. R., Sutcliffe J. G., Lo D. Mature microglia resemble immature antigen-presenting cells. Glia, 1998, 22 (1): 72-85.
66. Hickey W. F., Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science, 1988, 239 (4837) 290-292.
67. Becher B., Antel J. P. Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. Glia, 1996, 18 (1): 1-10.
68. Brosnan C. F., Raine C. S. Mechanisms of immune injury in multiple sclerosis. Brain Pathol., 1996, 6 (3): 243-257.
69. Hellings N., Raus J., Stinissen P. Insights into the immunopathogenesis of multiple sclerosis. Immunol. Res., 2002, 25 (1): 27-51.
70. Compston A. Remyelination of the central nervous system. Mult. Scler., 1996, 1 (6): 388-392.
71. Prineas J. W., Barnard R. O., Kwon E. E., Sharer L. R., Cho E. S. Multiple sclerosis remyelination of nascent lesions. Ann. Neurol., 1993, 33 (2): 137-151.
72. Raine C. S., Wu E. Multiple sclerosis: remyelination in acute lesions. J. Neuropathol. Exp. Neurol., 1993, 52 (3):, 199-204.
73. Scolding N., Franklin R., Stevens S., Heldin C. H., Comston A., Newcombe J. Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain, 1998, 121 (Pt 12): 2221-2228.
74. Perier O., Gregoire A. Electron microscopic features of multiple sclerosis lesions. Brain, 1965, 88 (5): 937-952.
75. Suzuki K., Andrews J. M., Waltz J. M., Terry R. D. Ultrastructural studies of multiple sclerosis. Lab. Invest., 1969, 20 (5): 444-454.
76. Zhao C., Fancy S. P., Kotter M. R., Li W. W., Franklin R. J. Mechanisms of CNS remyelination - the key to therapeutic advances. J. Neurol. Sci., 2005, 233 (1-2): 87-91.
77. Lucchinetti C. F., Brueck W., Rodriguez M., Lassmann H. Multiple sclerosis: lessons from neuropathology. Semin. Neurol., 1998, 18 (3): 337-349.
78. Kornek B., Lassmann H. Neuropathology of multiple sclerosis-new concepts. Brain Res. Bull., 2003, 61 (3): 321-326.
79. Bruck W., Bitsch A., Kolenda H., Bruck Y, Stiefel M., Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann. Neurol., 1997, 42 (5): 783-793.
80. Bitsch A., Schuchardt J., Bunkowski S., Kuhlmann T., Bruck W. Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain, 2000, 123 (Pt 6): 1174-1183.
81. Reindl M., Linington C., Brehm U., Egg R., Dilitz E., Deisenhammer F., Poewe W., Berger T. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain, 1999, 122 (Pt 11): 2047-2056.
82. Kornek B., Lassmann H. Axonal pathology in multiple sclerosis. A historical note. Brain Pathol., 1999, 9 (4): 651-656.
83. Ferguson B., Matyszak M. K., Esiri M. M., Perry V. H. Axonal damage in acute multiple sclerosis lesions. Brain, 1997, 120 (Pt 3): 393-399.
84. Trapp B. D., Peterson J., Ransohoff R. M., Rudick R., Mork S., Bo L. Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med., 1998, 338 (5): 278-285.
85. Kornek B., Storch M. K., Weissert R., Wallstroem E., Stefferl A., Olsson T., Linington C., Schmidbauer M., Lassmann H. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am. J. Pathol., 2000, 157 (1): 267-276.
86. Kuhlmann T., Lingfeld G., Bitsch A., Schuchardt J., Bruck W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain, 2002, 125 (Pt 10): 2202-2212.
87. Bjartmar C., Wujek J. R., Trapp B. D. Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J. Neurol. Sci., 2003, 206 (2): 165-171.
88. Trapp B. D., Ransohoff R., Rudick R. Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr. Opin. Neurol., 1999, 12 (3): 295-302.
89. Bjartmar C., Trapp B. D. Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Current Opinion in Neurology, 2001, 14 (3): 271-278.
90. Matthews P. M., De Stefano N., Narayanan S., Francis G. S., Wolinsky J. S., Antel J. P., Arnold D. L. Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin. Neurol., 1998, 18 (3): 327-336.
91. Hafler D. A. Multiple sclerosis. J. Clin. Invest., 2004, 113 (6): 788-794.
92. Pettinelli C. B., McFarlin D. E. Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2- T lymphocytes. J. Immunol., 1981, 127 (4): 1420-1423.
93. Huang D., Han Y, Rani M. R., Glabinski A., Trebst C., Sorensen T., Tani M., Wang J., Chien P., O'Bryan S., Bielecki B., Zhou Z. L., Majumder S., Ransohoff R. M. Chemokines and chemokine receptors in inflammation of the nervous system: manifold roles and exquisite regulation. Immunol. Rev., 2000, 177: 52-67.
94. Misu T., Onodera H., Fujihara K., Matsushima K., Yoshie O., Okita N., Takase S., Itoyama Y. Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis: imbalance of Th1/Th2-associated chemokine signaling. J. Neuroimmunol., 2001, 114 (1-2): 207-212.
95. Giunti D., Borsellino G., Benelli R., Marchese M., Capello E., Valle M. T., Pedemonte E., Noonan D., Albini A., Bernardi G., Mancardi G. L., Battistini L., Uccelli A. Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS. J. Leukoc. Biol., 2003, 73 (5): 584-590.
96. Babbe H., Roers A., Waisman A., Lassmann H., Goebels N., Hohlfeld R., Friese M., Schroder R., Deckert M., Schmidt S., Ravid R., Rajewsky K. Clonal expansions of CD8 (+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J. Exp. Med., 2000, 192 (3): 393-404.
97. GAY F. W., Drye T. J., Dick G. W., Esiri M. M. The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. Brain, 1997, 120 (Pt 8): 1461-1483.
98. Jacobsen M., Cepok S., Quak E., Happel M., Gaber R., Ziegler A., Schock S., Oertel W. H., Sommer N., Hemmer B. Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients. Brain, 2002, 125 (Pt 3): 538-550.
99. Skulina C., Schmidt S., Dornmair K., Babbe H., Roers A., Rajewsky K., Wekerle H., Hohlfeld R., Goebles N. Multiple sclerosis: brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood. Proc. Natl. Acad. Sci. USA, 2004, 101 (8): 2428-2433.
100. Jurewicz A., Biddison W. E., Antel J. P. MHC class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes. Journal of Immunology, 1998, 160 (6): 3056-3059.
101. Medana I. M., Gallimore A., Oxenius A., Martinic M. M., Wekerle H., Neumann H. MHC class I-restricted killing of neurons by virus-specific CD8+ T lymphocytes is effected through the Fas/FasL, but not the perforin pathway. Eur. J. Immunol., 2000, 30 (12): 3623-3633.
102. Crawford M. P., Yan S. X., Ortega S. B., Mehta R. S., Hewitt R. E., Price D. A., Stastny P., Douek D. C., Koup R. A., Racke M. K., Karandikar N. J. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay. Blood, 2004, 103 (11): 4222-4231.
103. Tsuchida T., Parker K. C., Turner R. V., McFarlnd H. F., Coligan J. E., Biddison W. E. Autoreactive CD8+ T-cell responses to human myelin protein-derived peptides. Proc. Natl. Acad. Sci. USA, 1994, 91 (23): 10859-10863.
104. Honma K., Parker K. C., Becker K. G., McFarland H. F., Coligan J. E., Biddison W. E. Identification of an epitope derived from human proteolipid protein that can induce autoreactive CD8+ cytotoxic T lymphocytes restricted by HLA- A3: evidence for cross-reactivity with an environmental microorganism. J. Neuroimmunol., 1997, 73 (1-2): 7-14.
105. Zang Y. C., Li S., Rivera V. M., Hong J., Robinson R. R., Breitbach W. T., Killian J., Zhang J. Z. Increased CD8+ cytotoxic T cell responses to myelin basic protein in multiple sclerosis. J. Immunol., 2004, 172 (8): 5120-5127.
106. Huseby E. S., Liggitt D., Brabb T., Schnabel B., Ohlen C., Goverman J. A pathogenic role for myelin-specific CD8 (+) T cells in a model for multiple sclerosis. J. Exp. Med., 2001, 194 (5): 669-676.
107. Steinman L. Myelin-specific CD8 T cells in the pathogenesis of experimental allergic encephalitis and multiple sclerosis. J. Exp. Med., 2001, 194 (5): F27-F30.
108. Dresse; A., Chin J. L., Sette A., Gausling R., Hollsberg P., Hafler D. A. Autoantigen recognition by human CD8 T cell clones: enhanced agonist response induced by altered peptide ligands. J. Immunol., 1997, 159 (10): 4943-4951.
109. Neumann H., Medana I. M., Bauer J., Lassmann H. Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci., 2002, 25 (6): 313-319.
110. Giuliani F., Goodyer C. G., Antel J. P., Yong V. W. Vulnerability of human neurons to T cell-mediated cytotoxicity. J. Immunol., 2003, 171 (1): 368-379.
111. Hellings N., Raus J., Stinissen P. T-cell vaccination in multiple sclerosis: update on clinical application and mode of action. Autoimmun. Rev., 2004, 3 (4): 267-275.
112. Fernandez O., Arbizu T., Izquerdo G., Martinez-Yelamos A., Gata J. M., Luque G., De Ramon E. Clinical benefits of interferon beta-la in relapsing-remitting MS: a phase IV study. Acta Neurol. Scand., 2003, 107 (1): 7-11.
113. Leary S. M., Thompson A. J. Interferon beta-la in primary progressive multiple sclerosis. J. Neurol. Sci., 2003, 206 (2): 215-216.
114. Paty D. W., Li D. K. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial., 1993 [classical article]. Neurology, 2001, 57 (12 Suppl. 5): S10-S15.
115. Paty D. W., Li D. K. Interferon beta- lb is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/ MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology, 1993, 43 (4): 662-667.
116. Yong V. W., Chabot S., Stuve O., Williams G. Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology, 1998, 51 (3): 682-689.
117. Dhib-Jalbut S. Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology, 2002, 58 (8 Suppl. 4): S3-S9.
118. Neuhaus O., Farina C., Wekerle H., Hohlfeld R. Mechanisms of action of glatiramer acetate in multiple sclerosis. Neurology, 2001, 56 (6): 702-708.
119. Ziemssen T., Kumpfel T., Klinkert W. E., Neuhaus O., Hohlfeld R. Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor. Brain, 2002, 125 (Pt 11): 2381-2391.
120. Chen M., Valenzuela R. M., Dhib-Jalbut S. Glatiramer acetate-reactive T cells produce brain derived neurotrophic factor. J. Neurol. Sci., 2003, 215 (1-2): 37-44.
121. THE IFNB Multiple Sclerosis Study Group. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology, 1993, 43 (4): 655-661.
122. THE IFNB Multiple Sclerosis Study Group and The University Of British Columbia MS/MRI Analysis Group. Interferon beta-lb in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology, 1995, 45 (7): 1277-1285.
123. Johnson K. P., Brooks B. R., Cohen J. A., Ford C. C., Goldstein J., Lisak R. P., Myers L. W., Panitch H. S., Rose J. W., Schiffer R. B. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology, 1995, 45 (7): 1268-1276.
124. Filippini G., Munari L., Incorvaia B., Ebers G. C., Polman C., D'Amico R., Rice G. P. Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet, 2003, 361 (9357): 545-552.
125. Cohen J. A., Cutter G. R., Fischer J. S., Goodman A. D., Heidenreich F. R., Kooijmans M. F., Sjandrock A. W., Rudick R. A., Simon J. H., Simonian N. A., Tsao E. C., Whitaker J. N. Benefit of interferon beta-la on MSFC progression in secondary progressive MS. Neurology, 2002, 59 (5): 679-687.
126. Polman C. H., Uitdehaag B. M. New and emerging treatment options for multiple sclerosis. Lancet Neurol., 2003, 2 (9): 563-566.
127. Jacobs L. D., Beck R. W., Simon J. H., Kinkel R. P., Browncheidle C. M., Murray T. J., Simonian N. A., Slasor P. J., Sandrock A. W. Intramuscular interferon beta-la therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N. Engl. J. Med., 2000, 343 (13): 898-904.
128. Comi G., Filippi M., Barkhof F., Durelli L., Edan G., Fernandez O., Hartung H., Seeldrayers P., Sorensen P. S., Rovaris M., Martinelli V., Hommes O. R. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet, 2001, 357 (9268): 1576-1582.
129. Hartung H. P., Gonsette R., Konig N., Kwiecinski H., GUSEO A., Morrissey S. P., Krapf H., Zwingers T. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet, 2002, 360 (9350): 2018-2025.
130. Edan G., Miller D., Clanet M., Confavreux C., Lyon-Caen O., Lubetzki C., Brochet B., Berry I., Rolland Y., Froment J. C., Cabanis E., Iba-Zizen M. T., Gandon J. M., Lai H. M., Moseley I., Sabouraud O. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J. Neurol. Neurosurg. Psychiatry, 1997, 62 (2): 112-118.
131. Hohlfeld R., Wieldl H. The ups and downs of multiple sclerosis therapeutics. Ann. Neurol., 2001, 49 (3): 281-284.
132. Hughes R. A. Immunotherapy for multiple sclerosis. J. Neurol. Neurosurg. Psychiatry, 1994, 57 (1): 3-6.
133. Barnes M. P., Bateman D. E., Cleland P. G., Dick D. J., Walls T. J., Newman P. K., Saunders M., Tilley P. J. Intravenous methylprednisolone for multiple sclerosis in relapse. J. Neurol. Neurosurg. Psychiatry, 1985, 48 (2): 157-159.
134. Milligan N. M., Newcombe R., Compston D. A. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects. J. Neurol. Neurosurg. Psychiatry, 1987, 50 (5): 511-516.
135. Blevins G., Martin R. Future immunotherapies in multiple sclerosis. Semin. Neurol., 2003, 23 (2): 147-158.
136. Zhang J. T-cell vaccination in multiple sclerosis: immunoregulatory mechanism and prospects for therapy. Crit. Rev. Immunol., 2001, 21 (1-3): 41-55.
137. Vandenbark A. A., Chou Y. K., Whitham R., Mass M., Buenafe A., Liefeld D., Kavanagh D., Cooper S., Hashim G. A., Offner H. Treatment of multiple sclerosis with T-cell receptor peptides: results of a double-blind pilot trial. Nat. Med., 1996, 2 (10): 1109-1115.
138. Bielekova B., Richert N., Howard T., Blevins G., Markovic-Plese S., McCartin J., Frank J. A., Wurfel J., Ohayon J., Waldmann T. A., McFarland H. F., Martin R. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc. Natl. Acad. Sci. USA, 2004, 101 (23): 8705-8708.
139. Miller D. H., Khan O. A., Sheremata W. A., Blumhardt L. D., Rice G. P., Libonati M. A., Willmer-Hulme A. J., Dalton C. M., Mizkiel K. A., O'Connor P. W. A controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med., 2003, 348 (1): 15-23.
140. Weber F., Polak T., Gunther A., Kubuschoi B., Janovskaja J., Bitsch A., Poser S., Rieckmann P. Synergistic immunomodulatory effects of interferon-betalb and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing-remitting multiple sclerosis. Ann. Neurol., 1998, 44 (1): 27-34.
141. Paolillo A., Coles A. J., Molyneux P. D., Gawne-Cain M., MacManus D., Barker G. J., Compston D. A., Miller D. H. Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology, 1999, 53 (4): 751-757.
142. Youssef S., Stuve O., Patarroyo J. C., Ruiz P. J., Radosevich J. L., Hur E. M., Bravo M., Mitchell D. J., Sobel R. A., Steinman L., Zamvil S. S. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature, 2002, 420 (6911): 78-84.
143. Pahan K., Namboodiri A. M., Sheikh F. G., Smith B. T., Singh I. Increasing cAMP attenuates induction of inducible nitric-oxide synthase in rat primary astrocytes. J. Biol. Chem., 1997, 272 (12): 7786-7791.
144. Weitz-Schmidt G., Welzenbach K., Brinkmann V., Kamata T., Kallen J., Bruns C., Cottens S., Takada Y., Hommel U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat. Med., 2001, 7 (6): 687-692.
145. Sicotte N. L., Liva S. M., Klutch R., Pfeiffer P., Bouvier S., Odesa S., Wu T. C., Voskuhl R. R. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann. Neurol., 2002, 52 (4): 421-428.
146. Duncan I. D., Grever W. E., Zhang S. C. Repair of myelin disease: strategies and progress in animal models. Mol. Med. Today, 1997, 3 (12): 554-561.
147. Franklin R. J. Remyelination of the demyelinated CNS: the case for and against transplantation of central, peripheral and olfactory glia. Brain Res. Bull., 2002, 57 (6): 827-832.
148. Baron-Van Evercooren A., Blakemore W. Remyelination through engraftment. In: Myelin biology and disorders. Lazzarini R. (ed). San Diego: Elsevier, 2004: 143-172.
149. Moscarello M. A., Mak B., Nguyen T. A., Wood D. D., Mastronardi F., Ludwin S. K. Paclitaxel (Taxol) attenuates clinical disease in a spontaneously demyelinating transgenic mouse and induces remyelination. Mult. Scler, 2002, 8 (2): 130-138.
150. Calabresi P. A., Wilterdink J. L., Rogg J. M., Mills P., Webb A., Whartenby K. A. An open label trial of combination therapy with interferon beta-la and oral methotrexate in MS. Neurology, 2002, 58 (2): 314-317.
151. Soos J. M., Stuve O., Youssef S., Bravo M., Johnson H. M., Weiner H. L., Zamvil S. S. Cutting edge: oral type I IFN-tau promotes a Th2 bias and enhances suppression of autoimmune encephalo myelitis by oral glatiramer acetate. J. Immunol., 2002, 169 (5): 2231-2235.