Heat Shock Protein 70: Roles in Multiple Sclerosis

Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE.

[1]  S. Khoury,et al.  Immunopathogenesis of multiple sclerosis. , 2012, Clinical immunology.

[2]  X. Montalban,et al.  Implication of the toll‐like receptor 4 pathway in the response to interferon‐β in multiple sclerosis , 2011, Annals of neurology.

[3]  Qiuyan Liu.  Triptolide and its expanding multiple pharmacological functions. , 2011, International immunopharmacology.

[4]  F. Geraci,et al.  Hsp70 and Its Molecular Role in Nervous System Diseases , 2011, Biochemistry research international.

[5]  G. Giovannoni,et al.  Smoking and Multiple Sclerosis: An Updated Meta-Analysis , 2011, PloS one.

[6]  K. Selmaj,et al.  Aberrant stress‐induced Hsp70 expression in immune cells in multiple sclerosis , 2010, Journal of neuroscience research.

[7]  S. Yokota,et al.  Cerebrospinal fluids containing anti-HSP70 autoantibodies from multiple sclerosis patients augment HSP70-induced proinflammatory cytokine production in monocytic cells , 2010, Journal of Neuroimmunology.

[8]  V. Apostolopoulos,et al.  A Heat Shock Protein 70-Based Vaccine with Enhanced Immunogenicity for Clinical Use , 2009, The Journal of Immunology.

[9]  I. Raskin,et al.  Oral administration of triptolide ameliorates the clinical signs of experimental autoimmune encephalomyelitis (EAE) by induction of HSP70 and stabilization of NF-κB/IκBα transcriptional complex , 2009, Journal of Neuroimmunology.

[10]  K. Mills,et al.  Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. , 2009, Immunity.

[11]  K. Moudgil,et al.  Heat-shock proteins can promote as well as regulate autoimmunity. , 2009, Autoimmunity reviews.

[12]  Mahavir Singh,et al.  IL-10 Is Critically Involved in Mycobacterial HSP70 Induced Suppression of Proteoglycan-Induced Arthritis , 2009, PloS one.

[13]  J. Stockman,et al.  Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study , 2009 .

[14]  Y. Mei,et al.  Triptolide modulates T‐cell inflammatory responses and ameliorates experimental autoimmune encephalomyelitis , 2008, Journal of neuroscience research.

[15]  D. Schoenfeld,et al.  Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis , 2008, Muscle & nerve.

[16]  C. Libert,et al.  A heat shock protein gene (Hsp70.1) is critically involved in the generation of the immune response to myelin antigen , 2008, European journal of immunology.

[17]  A. Rachitskaya,et al.  Cutting Edge: NKT Cells Constitutively Express IL-23 Receptor and RORγt and Rapidly Produce IL-17 upon Receptor Ligation in an IL-6-Independent Fashion1 , 2008, The Journal of Immunology.

[18]  Munitta Muthana,et al.  The dual immunoregulatory roles of stress proteins. , 2008, Trends in biochemical sciences.

[19]  P. Menheere,et al.  Vitamin D as an immune modulator in multiple sclerosis, a review , 2008, Journal of Neuroimmunology.

[20]  Yu-jia Yang,et al.  [Protective effects of heat shock preconditioning on the experimental autoimmune encephalomyelitis rats]. , 2007, Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics.

[21]  I. Cohen,et al.  Stress, Heat Shock Proteins, and Autoimmunity , 2007, Annals of the New York Academy of Sciences.

[22]  C. Brosnan,et al.  EAE Tolerance Induction with Hsp70-Peptide Complexes Depends on H60 and NKG2D Activity1 , 2007, The Journal of Immunology.

[23]  P. Gray,et al.  Extracellular Heat Shock Proteins in Cell Signaling and Immunity , 2007, Annals of the New York Academy of Sciences.

[24]  M. Jäättelä,et al.  The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions , 2007, FEBS letters.

[25]  C. Didelot,et al.  Apoptosis Versus Cell Differentiation , 2007, Prion.

[26]  R. Voellmy,et al.  Chaperone regulation of the heat shock protein response. , 2007, Advances in experimental medicine and biology.

[27]  A. Ascherio,et al.  Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. , 2006, JAMA.

[28]  D. Feinstein,et al.  The heat‐shock protein 90 inhibitor 17‐allylamino‐17‐demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitis , 2006, Journal of neurochemistry.

[29]  M. Jakowec,et al.  Association of MBP peptides with Hsp70 in normal appearing human white matter , 2006, Journal of the Neurological Sciences.

[30]  J. Gestwicki,et al.  Heat Shock Proteins 70 and 90 Inhibit Early Stages of Amyloid β-(1–42) Aggregation in Vitro* , 2006, Journal of Biological Chemistry.

[31]  A. Tzioufas,et al.  The Role of Chaperone Proteins in Autoimmunity , 2006, Annals of the New York Academy of Sciences.

[32]  J. Flynn,et al.  IL-17 Production Is Dominated by γδ T Cells rather than CD4 T Cells during Mycobacterium tuberculosis Infection1 , 2006, The Journal of Immunology.

[33]  R. Conwit,et al.  Neuroprotective agents for clinical trials in ALS , 2006, Neurology.

[34]  Y. Li,et al.  Generation of anti-tumor immunity using mammalian heat shock protein 70 DNA vaccines for cancer immunotherapy. , 2006, Vaccine.

[35]  Wei Tang,et al.  (5R)-5-Hydroxytriptolide (LLDT-8), a novel triptolide derivative, prevents experimental autoimmune encephalomyelitis via inhibiting T cell activation , 2006, Journal of Neuroimmunology.

[36]  S. Westerheide,et al.  Triptolide, an Inhibitor of the Human Heat Shock Response That Enhances Stress-induced Cell Death* , 2006, Journal of Biological Chemistry.

[37]  E. Frohman,et al.  Multiple sclerosis--the plaque and its pathogenesis. , 2006, The New England journal of medicine.

[38]  S. Yokota,et al.  Autoantibodies against HSP70 family proteins were detected in the cerebrospinal fluid from patients with multiple sclerosis , 2006, Journal of the Neurological Sciences.

[39]  C. Brosnan,et al.  Brain-Derived Heat Shock Protein 70-Peptide Complexes Induce NK Cell-Dependent Tolerance to Experimental Autoimmune Encephalomyelitis1 , 2006, The Journal of Immunology.

[40]  R. Conwit,et al.  Neuroprotective agents for clinical trials in ALS: a systematic assessment. , 2006, Neurology.

[41]  J. Flynn,et al.  IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. , 2006, Journal of immunology.

[42]  K. Ohtsuka,et al.  Inducers and co-inducers of molecular chaperones , 2005, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[43]  G. Multhoff,et al.  Alternative Mechanism by which IFN-γ Enhances Tumor Recognition: Active Release of Heat Shock Protein 721 , 2005, The Journal of Immunology.

[44]  M. Mason,et al.  Induction of heat shock proteins in B-cell exosomes , 2005, Journal of Cell Science.

[45]  M. Fleshner,et al.  Endogenous extra-cellular heat shock protein 72: Releasing signal(s) and function , 2005, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[46]  C. Gross,et al.  Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. , 2005, Cancer research.

[47]  S. Ludwin,et al.  Tissue preconditioning may explain concentric lesions in Baló's type of multiple sclerosis. , 2005, Brain : a journal of neurology.

[48]  J. Satoh,et al.  Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis , 2005, Neurobiology of Disease.

[49]  B. Prakken,et al.  Heat-shock proteins induce T-cell regulation of chronic inflammation , 2005, Nature Reviews Immunology.

[50]  F. Ritossa.  A new puffing pattern induced by temperature shock and DNP in drosophila , 1962, Experientia.

[51]  M. Mayer,et al.  Hsp70 chaperones: Cellular functions and molecular mechanism , 2005, Cellular and Molecular Life Sciences.

[52]  S. Andrew,et al.  Hsp70 release from peripheral blood mononuclear cells. , 2004, Biochemical and biophysical research communications.

[53]  P. Srivastava,et al.  The heat-shock protein receptors: some answers and more questions. , 2004, Tissue antigens.

[54]  A. Achiron,et al.  Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus , 2004, Clinical and experimental immunology.

[55]  C. Woolf,et al.  Adult neuron survival strategies — slamming on the brakes , 2004, Nature Reviews Neuroscience.

[56]  Nan Li,et al.  Triptolide (PG-490) induces apoptosis of dendritic cells through sequential p38 MAP kinase phosphorylation and caspase 3 activation. , 2004, Biochemical and biophysical research communications.

[57]  J. Dillner,et al.  An altered immune response to Epstein-Barr virus in multiple sclerosis , 2004, Neurology.

[58]  H. Beere.  `The stress of dying': the role of heat shock proteins in the regulation of apoptosis , 2004, Journal of Cell Science.

[59]  C. Drake,et al.  Glycoprotein 96 Can Chaperone Both MHC Class I- and Class II-Restricted Epitopes for In Vivo Presentation, but Selectively Primes CD8+ T Cell Effector Function 1 , 2004, The Journal of Immunology.

[60]  R. Morimoto,et al.  Molecular chaperones and the stress of oncogenesis , 2004, Oncogene.

[61]  Clare Baecher-Allan,et al.  Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis , 2004, The Journal of experimental medicine.

[62]  Robert H. Brown,et al.  Putting the heat on ALS , 2004, Nature Medicine.

[63]  Mihir S. Wagh,et al.  Immune modulation with high-dose heat-shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis. , 2004, International immunology.

[64]  Geoffrey Burnstock,et al.  Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice , 2004, Nature Medicine.

[65]  Jacek Szymanski,et al.  Inducible Heat Shock Protein 70 Promotes Myelin Autoantigen Presentation by the HLA Class II1 , 2004, The Journal of Immunology.

[66]  K. Walsh,et al.  Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed beta-amyloid in neurons. , 2004, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[67]  N. Secher,et al.  Exercise induces the release of heat shock protein 72 from the human brain in vivo , 2004, Cell stress & chaperones.

[68]  M. Salvetti,et al.  HSP70-1 promoter region polymorphism tested in three autoimmune diseases , 2004, Immunogenetics.

[69]  C. Milner,et al.  Structure and expression of the three MHC-linked HSP70 genes , 2004, Immunogenetics.

[70]  U. de Faire,et al.  Serum Heat Shock Protein 70 Levels Predict the Development of Atherosclerosis in Subjects With Established Hypertension , 2003, Hypertension.

[71]  Javed Khan,et al.  Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease. , 2003, Human molecular genetics.

[72]  Pritam Das,et al.  NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo , 2003 .

[73]  Qingbo Xu,et al.  Cross-Reactive B-Cell Epitopes of Microbial and Human Heat Shock Protein 60/65 in Atherosclerosis , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[74]  R. Pedotti,et al.  Response to Comment on "The Influence of the Proinflammatory Cytokine, Osteopontin, on Autoimmune Demyelinating Disease" , 2003, Science.

[75]  C. Brosnan,et al.  Heat shock protein 70 associations with myelin basic protein and proteolipid protein in multiple sclerosis brains. , 2003, International immunology.

[76]  Akihiko Takashima,et al.  Chaperones increase association of tau protein with microtubules , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[77]  M. Tsan,et al.  Endotoxin Contamination in Recombinant Human Heat Shock Protein 70 (Hsp70) Preparation Is Responsible for the Induction of Tumor Necrosis Factor α Release by Murine Macrophages* , 2003, The Journal of Biological Chemistry.

[78]  C. Gross,et al.  Heat shock protein 70-reactivity is associated with increased cell surface density of CD94/CD56 on primary natural killer cells , 2003, Cell stress & chaperones.

[79]  Pritam Das,et al.  NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. , 2003, The Journal of clinical investigation.

[80]  D. Lipsker,et al.  Endotoxin‐free heat‐shock protein 70 fails to induce APC activation , 2002, European journal of immunology.

[81]  F. Hartl,et al.  CD40, an extracellular receptor for binding and uptake of Hsp70–peptide complexes , 2002, The Journal of cell biology.

[82]  Michael Rehli,et al.  Novel Signal Transduction Pathway Utilized by Extracellular HSP70 , 2002, The Journal of Biological Chemistry.

[83]  P. Srivastava,et al.  Heat Shock Proteins gp96 and hsp70 Activate the Release of Nitric Oxide by APCs1 , 2002, The Journal of Immunology.

[84]  F. Hartl,et al.  Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein , 2002, Science.

[85]  J. Trojanowski,et al.  Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. , 2002, Science.

[86]  A. Compston,et al.  Multiple sclerosis. , 2002, Lancet.

[87]  John Q. Trojanowski,et al.  Chaperone Suppression of α-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease , 2001, Science.

[88]  I. Cohen,et al.  β-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial , 2001, The Lancet.

[89]  R. Sapolsky,et al.  Overexpression of HSP72 after Induction of Experimental Stroke Protects Neurons from Ischemic Damage , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[90]  M. Cheetham,et al.  In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance , 2001, Brain Research.

[91]  C. Whitacre.  Sex differences in autoimmune disease , 2001, Nature Immunology.

[92]  S. Kikuchi,et al.  Heat shock protein 70 gene polymorphism in Japanese patients with multiple sclerosis. , 2001, Tissue antigens.

[93]  R. Issels,et al.  The role of heat shock protein (hsp70) in dendritic cell maturation: Hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors , 2001, European journal of immunology.

[94]  D. Feinstein,et al.  The heat shock response reduces myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis in mice , 2001, Journal of neurochemistry.

[95]  P. Hooper,et al.  Heat shock proteins: new keys to the development of cytoprotective therapies , 2001, Expert opinion on therapeutic targets.

[96]  I. Cohen,et al.  Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial. , 2001, Lancet.

[97]  P. Srivastava,et al.  Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. , 2000, International immunology.

[98]  U. de Faire,et al.  Circulating heat shock protein 60 is associated with early cardiovascular disease. , 2000, Hypertension.

[99]  E. Wanker,et al.  Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[100]  J. Bajramovic,et al.  Differential expression of stress proteins in human adult astrocytes in response to cytokines , 2000, Journal of Neuroimmunology.

[101]  H. Rammensee,et al.  The heat shock protein gp96 induces maturation of dendritic cells and down‐regulation of its receptor , 2000, European journal of immunology.

[102]  F R Sharp,et al.  Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction , 2000, Annals of neurology.

[103]  Stuart K. Calderwood,et al.  HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine , 2000, Nature Medicine.

[104]  J. Rothman,et al.  Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[105]  Mahavir Singh,et al.  A Conserved Mycobacterial Heat Shock Protein (hsp) 70 Sequence Prevents Adjuvant Arthritis upon Nasal Administration and Induces IL-10-Producing T Cells That Cross-React with the Mammalian Self-hsp70 Homologue1 , 2000, The Journal of Immunology.

[106]  Yufei Wang,et al.  Heat shock proteins generate β‐chemokines which function as innate adjuvants enhancing adaptive immunity , 2000 .

[107]  B. Weinshenker,et al.  Multiple sclerosis. , 2000, The New England journal of medicine.

[108]  J. Corton,et al.  Elevated levels of circulating heat shock protein 70 (Hsp70) in peripheral and renal vascular disease , 2000, Heart and Vessels.

[109]  H. Kampinga,et al.  Heat shock protein 70 (Hsp70) stimulates proliferation and cytolytic activity of natural killer cells. , 1999, Experimental hematology.

[110]  M. Jäättelä,et al.  Heat shock proteins as cellular lifeguards. , 1999, Annals of medicine.

[111]  H Atlan,et al.  T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides. , 1999, Journal of autoimmunity.

[112]  A. Pockley,et al.  Identification of human heat shock protein 60 (Hsp60) and anti-Hsp60 antibodies in the peripheral circulation of normal individuals. , 1999, Cell stress & chaperones.

[113]  R. Morimoto,et al.  Regulation of the Heat Shock Transcriptional Response: Cross Talk between a Family of Heat Shock Factors, Molecular Chaperones, and Negative Regulators the Heat Shock Factor Family: Redundancy and Specialization , 2022 .

[114]  J. Corton,et al.  Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. , 1998, Immunological investigations.

[115]  Radhey S. Gupta,et al.  Heat shock proteins and experimental autoimmune encephalomyelitis II: environmental infection and extra-neuraxial inflammation alter the course of chronic relapsing encephalomyelitis , 1998, Journal of Neuroimmunology.

[116]  G. Bittner,et al.  Heat‐shock proteins in axoplasm: High constitutive levels and transfer of inducible isoforms from glia , 1998, The Journal of comparative neurology.

[117]  J. Sany,et al.  Gastric administration of recombinant 65 kDa heat shock protein delays the severity of type II collagen induced arthritis in mice. , 1998, The Journal of rheumatology.

[118]  L. Kotilinek,et al.  Heat Shock or Stress Proteins and Their Role As Autoantigens in Multiple Sclerosis , 1997, Annals of the New York Academy of Sciences.

[119]  L. Hightower,et al.  Variation in hsp gene expression and Hsp polymorphism: do they contribute to differential disease susceptibility and stress tolerance? , 1997, Cell stress & chaperones.

[120]  W. Tourtellotte,et al.  Multiple sclerosis: altered expression of 70- and 27-kDa heat shock proteins in lesions and myelin. , 1997, Journal of neuropathology and experimental neurology.

[121]  J. Foster,et al.  Differential induction of heat shock mRNA in oligodendrocytes, microglia, and astrocytes following hyperthermia. , 1997, Brain research. Molecular brain research.

[122]  C. Brosnan,et al.  Heat Shock Proteins and Multiple Sclerosis: A Review , 1996, Journal of neuropathology and experimental neurology.

[123]  C. Pozzilli,et al.  The immune response to Mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis , 1996, Journal of Neuroimmunology.

[124]  R. Anderson,et al.  A hitchhiker's guide to the human Hsp70 family. , 1996, Cell stress & chaperones.

[125]  P. Srivastava,et al.  A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. , 1995, Science.

[126]  R. Bell,et al.  Heat shock protein 70 gene polymorphisms and multiple sclerosis. , 1995, Tissue antigens.

[127]  D. Hafler,et al.  Increased frequency of gamma delta T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell receptor V gene rearrangements. , 1995, Journal of immunology.

[128]  C. Raine,et al.  Experimental autoimmune encephalomyelitis. Qualitative and semiquantitative differences in heat shock protein 60 expression in the central nervous system. , 1995, Journal of Immunology.

[129]  J. Strominger,et al.  Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein , 1995, Cell.

[130]  A. Sadovnick,et al.  Genetics of Multiple Sclerosis , 1998, Seminars in neurology.

[131]  J. Satoh,et al.  HSP72 induction by heat stress in human neurons and glial cells in culture , 1994, Brain Research.

[132]  M. Freedman,et al.  Cytokine induction of heat shock protein expression in human oligodendrocytes: An interleukin-1-mediated mechanism , 1994, Journal of Neuroimmunology.

[133]  D. Aquino,et al.  The 70‐kDa Heat Shock Cognate Protein (HSC70) Is a Major Constituent of the Central Nervous System and Is Up‐Regulated Only at the mRNA Level in Acute Experimental Autoimmune Encephalomyelitis , 1993, Journal of neurochemistry.

[134]  W. Welch,et al.  Heat shock proteins functioning as molecular chaperones: their roles in normal and stressed cells. , 1993, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[135]  P. Dore‐Duffy,et al.  Expression of endothelial cell activation antigens in microvessels from patients with multiple sclerosis. , 1993, Advances in Experimental Medicine and Biology.

[136]  M. Freedman,et al.  Differential expression of heat shock proteins by human glial cells , 1992, Journal of Neuroimmunology.

[137]  C. Pozzilli,et al.  T-lymphocyte reactivity to the recombinant mycobacterial 65- and 70-kDa heat shock proteins in multiple sclerosis. , 1992, Journal of autoimmunity.

[138]  Y. Shi,et al.  The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate , 1992, Molecular and cellular biology.

[139]  R. Morimoto,et al.  Effect of sodium salicylate on the human heat shock response. , 1992, Science.

[140]  J. Satoh,et al.  Heterogeneous induction of 72-kDa heat shock protein (HSP72) in cultured mouse oligodendrocytes and astrocytes , 1992, Brain Research.

[141]  M. Freedman,et al.  Peripheral blood γ‐δ T cells lyse fresh human brain—Derived oligodendrocytes , 1991 .

[142]  I. Brown,et al.  Expression of heat shock genes (hsp70) in the mammalian nervous system. , 1991, Results and problems in cell differentiation.

[143]  M. Freedman,et al.  Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes. , 1991, Annals of neurology.

[144]  W. Welch,et al.  Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly. , 1990, Science.

[145]  L. Steinman,et al.  The T lymphocyte in experimental allergic encephalomyelitis. , 1990, Annual review of immunology.

[146]  R. Young,et al.  T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65-kilodalton heat shock protein. , 1989, Journal of immunology.

[147]  J. Rothman,et al.  Peptide binding and release by proteins implicated as catalysts of protein assembly. , 1989, Science.

[148]  R. Young,et al.  Stress proteins may provide a link between the immune response to infection and autoimmunity. , 1989, International immunology.

[149]  H. Clark,et al.  The adoptive transfer of chronic relapsing experimental allergic encephalomyelitis with lymph node cells sensitized to myelin proteolipid protein , 1989, Journal of Neuroimmunology.

[150]  L. Hightower,et al.  Selective release from cultured mammalian cells of heat‐shock (stress) proteins that resemble glia‐axon transfer proteins , 1989, Journal of cellular physiology.

[151]  G. Blobel,et al.  70-kD heat shock-related protein is one of at least two distinct cytosolic factors stimulating protein import into mitochondria , 1988, The Journal of cell biology.

[152]  K. Riabowol,et al.  Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. , 1988, Science.

[153]  F. Breedveld,et al.  SYNOVIAL FLUID T CELL REACTIVITY AGAINST 65 kD HEAT SHOCK PROTEIN OF MYCOBACTERIA IN EARLY CHRONIC ARTHRITIS , 1988, The Lancet.

[154]  S. Lindquist,et al.  The heat-shock proteins. , 1988, Annual review of genetics.

[155]  R. Lasek,et al.  Heat shock-like protein is transferred from glia to axon , 1986, Brain Research.

[156]  R. Morimoto,et al.  Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[157]  R. Morimoto,et al.  Structure and expression of the human gene encoding major heat shock protein HSP70 , 1985, Molecular and cellular biology.

[158]  D. McFarlin,et al.  Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice , 1984, Nature.

[159]  Z. Werb,et al.  Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibroblasts. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[160]  J. Mussini,et al.  [Immunology of multiple sclerosis]. , 1982, La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris.

[161]  C. Pettinelli,et al.  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. , 1981, Journal of immunology.

[162]  A. Blalock.  Surgical treatment of pulmonary stenosis. , 1947, Lancet.