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Heat Shock Proteins and Multiple Sclerosis

  • Chapter
Stress Proteins

Abstract

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) with myelin damage (loss of myelin sheaths and eventually secondary axon damage). In most of cases it evolves from a relapsing-remitting phase to a chronic progressive one which brings about stable disability and handicap. In spite of the scanty certainties about its etiology, the pathogenesis of MS is widely accepted to be autoimmune based on:

  1. 1.

    A potentially disregulated immune response in patients compared to controls (the presence of immunocompetent cells not only inside the MS lesions but also as autoreactive, “in-vivo”-activated effectors in the peripheral blood or in the cerebrospinal fluid of patients; the presence of immuno-globulin oligoclonal bands in the cerebrospinal fluid of patients; the association with “at risk” MHC haplotypes in patients).

  2. 2.

    The pathogenetic role of such autoreactive effectors in studies on the animal model of MS, experimental allergic encephalomyelitis (EAE); in rodents and in primates, the encephalitogenicity of myelin-specific T lymphocytes (alone or in combination with myelin-specific antibodies) has been demonstrated.

  3. 3.

    Finally, and most importantly, the therapeutic efficacy of strategies aimed at deleting or antagonizing the pathogenic autoaggressive effectors; most of the treatments, recently implemented in MS with encouraging results, tend to modulate, more or less specifically, the disregulated immune response of the patients. Examples of such therapies include interferon ß, copolymer-1 and intravenous high-dose immunoglobulins.

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References

  • Allegretta M, Nicklas JA, Sriram S et al (1990) T cells responsive to myelin basic protein in patients with multiple scerosis. Science 247:718–721

    Article  PubMed  CAS  Google Scholar 

  • Amor S, Baker D, Layward L et al (1997) Multiple sclerosis: variations on a theme. Immunol Today 18:368–371

    Article  PubMed  CAS  Google Scholar 

  • Aquino DA, Klipfel AA, Brosnan CF, Norton WT (1993) The 70kDa heat shock cognate protein is a major constituent of the central nervous system and is upregulated only at the mRNA level in acute experimental autoimmune encephalomyelitis. J Neurochem 61:1340–1348

    Article  PubMed  CAS  Google Scholar 

  • Aquino DA, Lopez C., Farooq M (1996) Antisense oligonucleotide to the 70-kDa heat shock protein inhibits synthesis of myelin basic protein. Neurochem Res 21:417–422

    Article  PubMed  CAS  Google Scholar 

  • Aquino DA, Capello E, Weisstein J et al (1997) Multiple sclerosis: altered expression of 70-and 27-kDa heat shock proteins in lesions and myelin. J Neuropathol Exp Neurol 56:664–672

    PubMed  CAS  Google Scholar 

  • Bajramovic JJ, Lassmann H, van Noort JM (1997) Expression of αB-crystallin in glia cells during lesional development in multiple sclerosis. J Neuroimmunol 78:143–151

    Article  PubMed  CAS  Google Scholar 

  • Battistini L, Salvetti M, Ristori G et al. (1995a) HSP70 selects for an oligoclonal Vδ2-Jδ3 T cell receptor response in lymphocytes from healthy individuals, multiple sclerosis and tuberculosis patients. Mol Med 1:554–562

    PubMed  CAS  Google Scholar 

  • Battistini L, Selmaj K, Kowal C et al (1995b) Multiple sclerosis: limited diversity of the Vδ2-Jδ3 T-cell receptor in chronic-active lesions. Ann Neurol 37:198–205

    Article  PubMed  CAS  Google Scholar 

  • Birnbaum G, Kotilinek L, Albrecht L (1993) Spinal fluid lymphocytes from a subgroup of multiple sclerosis patients respond to mycobacterial antigens. Ann Neurol 34:18–24

    Article  PubMed  CAS  Google Scholar 

  • Birnbaum G, Kotilinek L, Schlievert P et al (1996) Heat shock proteins and experimental autoimmune encephalomyelitis (EAE): I. Immunization with a peptide of the myelin protein 2′, 3′ cyclic nucleotide 3′ phosphodiesterase that is cross-reactive with a heat shock protein alters the course of EAE. J Neurosci Res 44:381–396

    Google Scholar 

  • Brosnan CF, Battistini L, Gao YL, Raine CS, Aquino DA (1996) Heat shock proteins and multiple sclerosis. J Neuropathol Exp Neurol 55:389–402

    Article  PubMed  CAS  Google Scholar 

  • Cascino I, Galeazzi M, Salvetti M et al (1994) HSP70-1 promoter region polymorphisms tested in three autoimmune diseases. Immunogenetics 39:291–293

    Article  PubMed  CAS  Google Scholar 

  • Cohen IR (1992a) The cognitive principle challenges clonal selection. Immunol Today 13:441–444

    Article  PubMed  CAS  Google Scholar 

  • Cohen IR (1992b) The cognitive paradigm and the immunological homunculus. Immunol Today 13:490–494

    Article  PubMed  CAS  Google Scholar 

  • de Graeff-Meeder ER, van Eden W, Rijkers GT et al (1995) Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis. J Clin Invest 95:934–940

    Article  PubMed  Google Scholar 

  • D′Souza SD, Antel JP, Freedman MS (1994) Cytokine induction of heat shock protein expression in human oligodendrocytes: an interleukin-1 mediated mechanism. J Neuroimmunol 50:17–24

    Article  PubMed  Google Scholar 

  • Feinstein DL, Galea E, Aquino DA et al (1996) Heat shock protein 70 suppresses astroglial-inducible nitric-oxide synthase expression by decreasing NFkappaB activation. J Biol Chem 271:17724–17732

    Article  PubMed  CAS  Google Scholar 

  • Fiori P, Ristori G, Cacciani A et al (1997) Down-regulation of cell-surface CD4 coreceptor expression and modulation of experimental allergic encephalomyelitis. Int Immunol 9:541–545

    Article  PubMed  CAS  Google Scholar 

  • Freedman MS, Ruijs TCG, Selin LK et al (1991) Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes. Ann Neurol 30:794–800

    Article  PubMed  CAS  Google Scholar 

  • Freedman MS, Buu NN, Ruijs TC., Williams K, Antel JP (1992) Differential expression of heat shock proteins by human glial cells. J Neuroimmunol 41:231–238

    Article  PubMed  CAS  Google Scholar 

  • Freedman MS, D’Souza S, Antel JP (1997) Gamma delta T-cell-human glial cell interaction I. In vitro induction of gamma delta T cell expansion by human glial cells. J Neuroimmunol 74:135–142

    Article  PubMed  CAS  Google Scholar 

  • Gao YL, Raine CS, Brosnan CF (1994) Humoral response to hsp 65 in multiple sclerosis and other neurological conditions. Neurology 44:941–946

    Article  PubMed  CAS  Google Scholar 

  • Gao YL, Brosnan CF, Raine CS (1995) Experimental autoimmune encephalomyelitis. Qualitative and quantitative differences in heat shock protein 60 expression in the central nervous system. J Immunol 154:3448–3456

    Google Scholar 

  • Goverman J, Woods A, Larson L et al (1993) Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72:551–560

    Article  PubMed  CAS  Google Scholar 

  • Gray D, Matzinger P (1991) T cell memory is short lived in the absence of antigen. J Exp Med 174:969–974

    Article  PubMed  CAS  Google Scholar 

  • Gupta RS, Bhag S (1992) Cloning of the HSP70 gene from Halobacterium marismortui: relatedness of archaebacterial HSP70 to its eubacterial homologs and a model for the evolution of the HSP70 gene. J Bacteriol 174:4594–4605

    PubMed  CAS  Google Scholar 

  • Gupta RS, Golding GB (1993) Evolution of HSP70 gene and its implications regarding relationships between archaebacteria, eubacteria and eukaryotes. J Mol Evol 37:573–582

    Article  PubMed  CAS  Google Scholar 

  • Head MW, Corbin E, Goldman JE (1993) Overexpression and abnormal modification of the stress proteins alpha-B crystallin and HSP27 in Alexander disease. Am J Pathol 143:1743–1753

    PubMed  CAS  Google Scholar 

  • Holfeld R (1997) Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives. Brain 120:865–916

    Article  Google Scholar 

  • Jaattela M, Saksela K, Saksela E (1989) Heat shock protects WEHI-164 target cells from the cytolysis by tumor necrosis factor a and ß. Eur J Immunol 19:1413–1417

    Article  PubMed  CAS  Google Scholar 

  • Kaufman DL, Clare-Salzler M, Tian J (1993) Spontaneous loss of T cell tolerance to glutamic acid decarboxylase in murine insulin dependent diabetes. Nature 366:69–72

    Article  PubMed  CAS  Google Scholar 

  • Kaufmann SH (1994) Heat shock proteins and autoimmunity. Intl Arch All Immunol 103:317–322

    Article  CAS  Google Scholar 

  • Koga T, Wand-Wurttenberger A, de Bruyn J, Munk ME, Schoel B, Kaufmann SH (1989) T cells against a bacterial heat shock protein recognize stressed macrophages. Sciences 246:1112–1115

    Article  Google Scholar 

  • Kojima K, Berger T, Lassmann H et al (1994) Experimental autoimmune panencephalitis and uveoretinitis transferred to the Lewis rat by T lymphocytes specific for the S100/3 molecule, a calcium binding protein of astroglia. J Exp Med 180:817–829

    Article  PubMed  CAS  Google Scholar 

  • Kurtzke JF (1992) Epidemiologie evidence for multiple sclerosis as an infection. Clin Microbiol Rev 6:382–427

    Google Scholar 

  • Lehmann PV, Forsthuber T, Miller A, Sercarz EE (1992) Spreading of T cell autoimmunity to cryptic determinants of an autoantigen. Nature 358:155–157

    Article  PubMed  CAS  Google Scholar 

  • Lowe J, McDermott H, Pike I, Spendlove I, Landon M, Mayer RJ (1992) Alpha-B crystallin expression in non-lenticular tissues and selective presence in ubiquitinated inclusion bodies in human diseases. J Pathol 166:61–68

    Article  PubMed  CAS  Google Scholar 

  • Mehlen P, Preville X, Chareyron P et al (1995a) Constitutive expression of human hsp27, Drosophila hasp27, or human alpha-B crystallin confers resistance to TNF-and oxidative stress-induced cytotoxicity in stably tranfected murine L929 fibro-blasts. J Immunol 154:363–374

    PubMed  CAS  Google Scholar 

  • Mehlen P, Mehlen A, Guillet D et al (1995b) Tumor necrosis factor-alpha induced changes in the phosphorylation, cellular localization, and oligomerization of human hsp27, a stress protein that confers cellular resistance to this cytokine. J Cell Biochem 58:248–259

    Article  PubMed  CAS  Google Scholar 

  • Mor F, Cohen IR (1992) T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock protein. J Clin Invest 90:2447–2455

    Article  PubMed  CAS  Google Scholar 

  • Newcomb JR, Cresswell P (1993) Characterization of endogenous peptides bound to purified HLA-DR molecules and their absence from invariant chain-associated αβ dimers. J Immunol 150:499–507

    PubMed  CAS  Google Scholar 

  • Olsson T, Sun J, Hiflert J et al (1992) Increased numbers of T cells recognizing multiple myelin basic protein-epitopes in multiple sclerosis. Eur J Immunol 22:1083–1087

    Article  PubMed  CAS  Google Scholar 

  • Pluschke G, Ruegg D, Hohlfeld R et al (1992) Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor. J Exp Med 176:1785–1793

    Article  PubMed  CAS  Google Scholar 

  • Porcelli SA, Morita CT, Modlin PL (1996) T cell recognition of non-peptide antigens. Curr Opin Immunol 8:510–516

    Article  PubMed  CAS  Google Scholar 

  • Prabhakar, S Kurien E, Gupta RS et al (1994) Heat shock protein immunoreactivity in CSF: correlation with oligoclonal banding and demyelinating disease. Neurology 44:1644–1648

    Article  PubMed  CAS  Google Scholar 

  • Ragheb S, Lisak RP (1993) Multiple sclerosis: genetic background versus environment. Ann Neurol 34:509–510

    Article  PubMed  CAS  Google Scholar 

  • Raine CS (1994a) Immune system molecule expression in the central nervous system. J Neuropath Exp Neurol 53:328–337

    Article  PubMed  CAS  Google Scholar 

  • Raine CS (1994b) The Dale E. McFarlin memorial lecture: the immunology of the multiple sclerosis. Ann Neurol 36:S61–S72

    Article  PubMed  CAS  Google Scholar 

  • Rajan AJ, Gao YL, Raine CS et al (1996) A pathogenic role for gamma delta T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse. J Immunol 157:941–949

    PubMed  CAS  Google Scholar 

  • Ramachandran S, Bell RB (1995) Heavy shock protein 70 gene polymorphisms and multiple sclerosis. Tissue Antigens 46:140–141

    Article  PubMed  CAS  Google Scholar 

  • Salvetti M, Buttinelli C., Ristori G et al (1992) T-lymphocyte reactivity to the recombinant mycobacterial 65-and 70-kD heat shock proteins in multiple sclerosis. J Autoimmun 5:691–702

    Article  PubMed  CAS  Google Scholar 

  • Salvetti M, Ristori G, Buttinelli C et al (1996) The immune response to mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis. J Neuroimmunol 65:143–153

    Article  PubMed  CAS  Google Scholar 

  • Satoh J, Kim SU (1994) HSP induction by heat stress in human neurons and glial cells in culture. Brain Res 653:243–250

    Article  PubMed  CAS  Google Scholar 

  • Satoh J, Kim SU (1995a) Constitutive and inducible expression of heat shock protein HSP72 in oligodendrocytes in culture. Neuroreport 6:1081–1084

    Article  PubMed  CAS  Google Scholar 

  • Satoh J, Kim SU (1995b) Cytokines and growth factors induce HSP72 phosphorylation in human astrocytes. J Neuropath Exp Neurol 54:504–512

    Article  PubMed  CAS  Google Scholar 

  • Satoh J, Nomaguchi H, Tabira T (1992a) Constitutive expression of 65-kDa heat shock protein-like immunoreactivity in cultured mouse oligodendrocytes. Brain Res 595:281–290

    Article  PubMed  CAS  Google Scholar 

  • Satoh J, Yamamura T, Kunishita T, Tabira T (1992b) Heterogeneous induction of 72-kDa heat shock protein (HSP72) in cultured mouse oligodendrocytes and astrocytes. Brain Res 573:37–43

    Article  PubMed  CAS  Google Scholar 

  • Satoh J, Tabira T, Yamamura T, Kim SU (1994) HSP72 induction by heat stress is not universal in mammalian neural cell lines. J Neurosci Res 37:44–53

    Article  PubMed  CAS  Google Scholar 

  • Selmaj K, Brosnan CF, Raine CS (1991) Colocalization of lymphocytes bearing the γδ T cell receptor and heat shock protein 65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci USA 88:6452–6456

    Article  PubMed  CAS  Google Scholar 

  • Shinohara H, Inaguma Y, Goto S, Inagaki T, Kato K (1993) Alpha-B crystallin and HSP28 are enhanced in the cerebral cortex of patients with Alzheimer’s disease. J Neurol Sci 119:203–208

    Article  PubMed  CAS  Google Scholar 

  • Stinissen P, Vandevyver C., Medaer R et al (1995) Increased frequency of gd T cells in the cerebrospinal fluid and peripheral blood of patients with multiple sclerosis: reactivity, cytotoxicity and T cell receptor V gene rearrangements. J Immunol 154:4883–4894

    PubMed  CAS  Google Scholar 

  • van Noort JM, van Sechel AC., Bajramovic JJ, el Ouagmin M, Polman CH, Lassmann H, Ravid R (1995) The small heat shock protein alpha-B crystallin as a candidate autoantigen in multiple sclerosis. Nature 375:798–801

    Article  PubMed  Google Scholar 

  • Williams GT, Smith TA, Spooncer E et al (1990) Haematopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 343:76–79

    Article  PubMed  CAS  Google Scholar 

  • Wucherpfennig KW, Weiner HL, Hafler DA (1991) T cell recognition of myelin basic protein. Immunol Today 12:277–282

    Article  PubMed  CAS  Google Scholar 

  • Wucherpfennig KW, Newcombe J, Li H, Keddy C., Cuzner ML, Hafler DA (1992) γδ T-cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sei USA 89:4588–4592

    Article  CAS  Google Scholar 

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Ristori, G. et al. (1999). Heat Shock Proteins and Multiple Sclerosis. In: Latchman, D.S. (eds) Stress Proteins. Handbook of Experimental Pharmacology, vol 136. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58259-2_17

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  • DOI: https://doi.org/10.1007/978-3-642-58259-2_17

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