Role of the innate immune system in the pathogenesis of multiple sclerosis

Airas, 2008, Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells, Clin. Exp. Immunol., 151, 235, 10.1111/j.1365-2249.2007.03555.x Andersson, 2008, Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis, J. Leukoc. Biol., 84, 1248, 10.1189/jlb.1207844 Angelini, 2004, FcgammaRIII discriminates between 2 subsets of Vgamma9Vdelta2 effector cells with different responses and activation pathways, Blood, 104, 1801, 10.1182/blood-2004-01-0331 Araki, 2003, Th2 bias of CD4+ NKT cells derived from multiple sclerosis in remission, Int. Immunol., 15, 279, 10.1093/intimm/dxg029 Aravalli, 2007, Toll-like receptors in defense and damage of the central nervous system, J. Neuroimmune Pharmacol., 2, 297, 10.1007/s11481-007-9071-5 Bailey, 2007, CNS myeloid DCs presenting endogenous myelin peptides ‘preferentially’ polarize CD4+ T(H)-17 cells in relapsing EAE, Nat. Immunol., 8, 172, 10.1038/ni1430 Baker, 1991, Cytokines in the central nervous system of mice during chronic relapsing experimental allergic encephalomyelitis, Cell Immunol., 134, 505, 10.1016/0008-8749(91)90321-2 Bauer, 1994, Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis, J. Neurosci. Res., 38, 365, 10.1002/jnr.490380402 Bennett, 2009, Bone marrow-derived mast cells accumulate in the central nervous system during inflammation but are dispensable for experimental autoimmune encephalomyelitis pathogenesis, J. Immunol., 182, 5507, 10.4049/jimmunol.0801485 Benveniste, 1997, Cytokines: influence on glial cell gene expression and function, Chem. Immunol., 69, 31, 10.1159/000058653 Bettelli, 2008, Induction and effector functions of T(H)17 cells, Nature, 453, 1051, 10.1038/nature07036 Bettelli, 2004, Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis, J. Exp. Med., 200, 79, 10.1084/jem.20031819 Bielekova, 2006, Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis, Proc. Natl. Acad. Sci. U. S. A., 103, 5941, 10.1073/pnas.0601335103 Bsibsi, 2002, Broad expression of Toll-like receptors in the human central nervous system, J. Neuropathol. Exp. Neurol., 61, 1013, 10.1093/jnen/61.11.1013 Chen, 2008, Correlation of specialized CD16(+) gammadelta T cells with disease course and severity in multiple sclerosis, J. Neuroimmunol., 194, 147, 10.1016/j.jneuroim.2007.11.010 Christy, 2007, The multitasking mast cell: positive and negative roles in the progression of autoimmunity, J. Immunol., 179, 2673, 10.4049/jimmunol.179.5.2673 Cooper, 2001, The biology of human natural killer-cell subsets, Trends Immunol., 22, 633, 10.1016/S1471-4906(01)02060-9 Cooper, 2001, Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset, Blood, 97, 3146, 10.1182/blood.V97.10.3146 Darlington, 2008, Innate immune-mediated neuronal injury consequent to loss of astrocytes, J. Neuropathol. Exp. Neurol., 67, 590, 10.1097/NEN.0b013e3181772cf6 De Jager, 2008, Cytometric profiling in multiple sclerosis uncovers patient population structure and a reduction of CD8low cells, Brain, 131, 1701, 10.1093/brain/awn118 Debouverie, 2008, Natural history of multiple sclerosis in a population-based cohort, Eur. J. Neurol., 15, 916, 10.1111/j.1468-1331.2008.02241.x Della Chiesa, 2006, Multidirectional interactions are bridging human NK cells with plasmacytoid and monocyte-derived dendritic cells during innate immune responses, Blood, 108, 3851, 10.1182/blood-2006-02-004028 Della Chiesa, 2003, The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors, Eur. J. Immunol., 33, 1657, 10.1002/eji.200323986 Dittel, 1999, Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis, J. Immunol., 163, 32, 10.4049/jimmunol.163.1.32 El Behi, 2005, New insights into cell responses involved in experimental autoimmune encephalomyelitis and multiple sclerosis, Immunol. Lett., 96, 11, 10.1016/j.imlet.2004.07.017 Ferlazzo, 2002, Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells, J. Exp. Med., 195, 343, 10.1084/jem.20011149 Fernandez, 1999, Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo, Nat. Med., 5, 405, 10.1038/7403 Freedman, 1997, gamma delta T-cell-human glial cell interactions. II. Relationship between heat shock protein expression and susceptibility to cytolysis, J. Neuroimmunol., 74, 143, 10.1016/S0165-5728(96)00218-4 Freedman, 1997, gamma delta T-cell-human glial cell interactions. I. In vitro induction of gammadelta T-cell expansion by human glial cells, J. Neuroimmunol., 74, 135, 10.1016/S0165-5728(96)00217-2 Freedman, 1991, Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes, Ann. Neurol., 30, 794, 10.1002/ana.410300608 Furlan, 2003, Activation of invariant NKT cells by alphaGalCer administration protects mice from MOG35-55-induced EAE: critical roles for administration route and IFN-gamma, Eur. J. Immunol., 33, 1830, 10.1002/eji.200323885 Galazka, 2007, EAE tolerance induction with Hsp70-peptide complexes depends on H60 and NKG2D activity, J. Immunol., 179, 4503, 10.4049/jimmunol.179.7.4503 Gerosa, 2002, Reciprocal activating interaction between natural killer cells and dendritic cells, J. Exp. Med., 195, 327, 10.1084/jem.20010938 Gilliet, 2002, Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells, J. Exp. Med., 195, 695, 10.1084/jem.20011603 Gray, 2008, Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis, Brain Pathol., 18, 86, 10.1111/j.1750-3639.2007.00110.x Gregory, 2005, Mast cells are required for optimal autoreactive T cell responses in a murine model of multiple sclerosis, Eur. J. Immunol., 35, 3478, 10.1002/eji.200535271 Hammarberg, 2000, Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells, J. Neurosci., 20, 5283, 10.1523/JNEUROSCI.20-14-05283.2000 Hayday, 2000, [gamma][delta] cells: a right time and a right place for a conserved third way of protection, Annu. Rev. Immunol., 18, 975, 10.1146/annurev.immunol.18.1.975 Hirata, 2005, Prevention of experimental autoimmune encephalomyelitis by transfer of embryonic stem cell-derived dendritic cells expressing myelin oligodendrocyte glycoprotein peptide along with TRAIL or programmed death-1 ligand, J. Immunol., 174, 1888, 10.4049/jimmunol.174.4.1888 Huang, 2006, The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system, Faseb. J., 20, 896, 10.1096/fj.05-5465com Huang, 1999, Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines, J. Neuroimmunol., 99, 82, 10.1016/S0165-5728(99)00106-X Hur, 2007, Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells, Nat. Immunol., 8, 74, 10.1038/ni1415 Illes, 2000, Differential expression of NK T cell V alpha 24J alpha Q invariant TCR chain in the lesions of multiple sclerosis and chronic inflammatory demyelinating polyneuropathy, J. Immunol., 164, 4375, 10.4049/jimmunol.164.8.4375 Jack, 2007, Th1 polarization of CD4+ T cells by Toll-like receptor 3-activated human microglia, J. Neuropathol. Exp. Neurol., 66, 848, 10.1097/nen.0b013e3181492a7 Johnson, 1988, The role of mast cells in demyelination. 1. Myelin proteins are degraded by mast cell proteases and myelin basic protein and P2 can stimulate mast cell degranulation, Brain Res, 444, 195, 10.1016/0006-8993(88)90929-8 Karni, 2006, Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response, J. Immunol., 177, 4196, 10.4049/jimmunol.177.6.4196 Kastrukoff, 2003, Clinical relapses of multiple sclerosis are associated with ‘novel’ valleys in natural killer cell functional activity, J. Neuroimmunol., 145, 103, 10.1016/j.jneuroim.2003.10.001 Kastrukoff, 1998, A role for natural killer cells in the immunopathogenesis of multiple sclerosis, J. Neuroimmunol., 86, 123, 10.1016/S0165-5728(98)00014-9 Katz-Levy, 2000, Temporal development of autoreactive Th1 responses and endogenous presentation of self myelin epitopes by central nervous system-resident APCs in Theiler's virus-infected mice, J. Immunol., 165, 5304, 10.4049/jimmunol.165.9.5304 Kawanokuchi, 2008, Production and functions of IL-17 in microglia, J. Neuroimmunol., 194, 54, 10.1016/j.jneuroim.2007.11.006 Kempuraj, 2008, Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell-dependent stimulation of Jurkat T cells, Br. J. Pharmacol., 155, 1076, 10.1038/bjp.2008.356 Khoury, 1995, Mechanisms of acquired thymic tolerance in experimental autoimmune encephalomyelitis: thymic dendritic-enriched cells induce specific peripheral T cell unresponsiveness in vivo, J. Exp. Med., 182, 357, 10.1084/jem.182.2.357 Kobayashi, 1997, Aggravation of murine experimental allergic encephalomyelitis by administration of T-cell receptor gammadelta-specific antibody, J. Neuroimmunol., 73, 169, 10.1016/S0165-5728(96)00187-7 Korn, 2007, Th17 cells: effector T cells with inflammatory properties, Semin. Immunol., 19, 362, 10.1016/j.smim.2007.10.007 Kutzelnigg, 2005, Cortical demyelination and diffuse white matter injury in multiple sclerosis, Brain, 128, 2705, 10.1093/brain/awh641 Lee, 2002, Toll-like receptors and inflammation in the CNS, Curr. Drug Targets Inflamm. Allergy, 1, 181, 10.2174/1568010023344698 Li, 2006, Dendritic cells transduced with SOCS-3 exhibit a tolerogenic/DC2 phenotype that directs type 2 Th cell differentiation in vitro and in vivo, J. Immunol., 177, 1679, 10.4049/jimmunol.177.3.1679 Lipscomb, 2002, Dendritic cells: immune regulators in health and disease, Physiol. Rev., 82, 97, 10.1152/physrev.00023.2001 Lock, 2002, Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis, Nat. Med., 8, 500, 10.1038/nm0502-500 Logothetis, 2005, A pilot, open label, clinical trial using hydroxyzine in multiple sclerosis, Int. J. Immunopathol. Pharmacol., 18, 771, 10.1177/039463200501800421 Lucas, 2007, Dendritic cells prime natural killer cells by trans-presenting interleukin 15, Immunity, 26, 503, 10.1016/j.immuni.2007.03.006 Lunemann, 2008, Human NK cells kill resting but not activated microglia via NKG2D- and NKp46-mediated recognition, J. Immunol., 181, 6170, 10.4049/jimmunol.181.9.6170 MacDonald, 2002, Characterization of human blood dendritic cell subsets, Blood, 100, 4512, 10.1182/blood-2001-11-0097 Malaviya, 1996, Mast cells process bacterial Ags through a phagocytic route for class I MHC presentation to T cells, J. Immunol., 156, 1490, 10.4049/jimmunol.156.4.1490 Mars, 2002, Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice, J. Immunol., 168, 6007, 10.4049/jimmunol.168.12.6007 Marta, 2008, Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis, Eur. J. Immunol., 38, 565, 10.1002/eji.200737187 Marta, 2009, Regulation of autoimmune encephalomyelitis by toll-like receptors, Autoimmun. Rev., 8, 506, 10.1016/j.autrev.2009.01.006 Matsumoto, 1998, Role of natural killer cells and TCR gamma delta T cells in acute autoimmune encephalomyelitis, Eur. J. Immunol., 28, 1681, 10.1002/(SICI)1521-4141(199805)28:05<1681::AID-IMMU1681>3.0.CO;2-T McMahon, 2005, Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis, Nat. Med., 11, 335, 10.1038/nm1202 Medic, 2008, Mast cell activation by myelin through scavenger receptor, J. Neuroimmunol., 200, 27, 10.1016/j.jneuroim.2008.05.019 Menges, 2002, Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity, J. Exp. Med., 195, 15, 10.1084/jem.20011341 Miller, 2007, Antigen presentation in the CNS by myeloid dendritic cells drives progression of relapsing experimental autoimmune encephalomyelitis, Ann. N. Y. Acad. Sci., 1103, 179, 10.1196/annals.1394.023 Mix, 1990, CD4+, CD8+, and CD4- CD8- T cells in CSF and blood of patients with multiple sclerosis and tension headache, Scand. J. Immunol., 31, 493, 10.1111/j.1365-3083.1990.tb02797.x Monney, 2002, Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease, Nature, 415, 536, 10.1038/415536a Morandi, 2008, Role of natural killer cells in the pathogenesis and progression of multiple sclerosis, Pharmacol. Res., 57, 1, 10.1016/j.phrs.2007.11.003 Moretta, 2008, NK cells at the interface between innate and adaptive immunity, Cell Death Differ., 15, 226, 10.1038/sj.cdd.4402170 Moretta, 2006, Effector and regulatory events during natural killer-dendritic cell interactions, Immunol. Rev., 214, 219, 10.1111/j.1600-065X.2006.00450.x Murugaiyan, 2008, Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis, J. Immunol., 181, 7480, 10.4049/jimmunol.181.11.7480 Napoli, 2009, Microglial clearance function in health and disease, Neuroscience, 158, 1030, 10.1016/j.neuroscience.2008.06.046 Napoli, 2009, Protective effects of microglia in multiple sclerosis, Exp. Neurol. Odyniec, 2004, Gammadelta T cells enhance the expression of experimental autoimmune encephalomyelitis by promoting antigen presentation and IL-12 production, J. Immunol., 173, 682, 10.4049/jimmunol.173.1.682 Olive, 1995, Gamma delta T cell receptor variable region usage during the development of experimental allergic encephalomyelitis, J. Neuroimmunol., 62, 1, 10.1016/0165-5728(95)00081-C Olsson, 1974, Mast cells in plaques of multiple sclerosis, Acta Neurol. Scand., 50, 611, 10.1111/j.1600-0404.1974.tb02806.x Pal, 2001, Costimulation-dependent modulation of experimental autoimmune encephalomyelitis by ligand stimulation of V alpha 14 NK T cells, J. Immunol., 166, 662, 10.4049/jimmunol.166.1.662 Peritt, 1998, Differentiation of human NK cells into NK1 and NK2 subsets, J. Immunol., 161, 5821, 10.4049/jimmunol.161.11.5821 Piccio, 2008, Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation, Brain, 131, 3081, 10.1093/brain/awn217 Piccio, 2007, Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis, Eur. J. Immunol., 37, 1290, 10.1002/eji.200636837 Piccioli, 2002, Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells, J. Exp. Med., 195, 335, 10.1084/jem.20010934 Ponomarev, 2005, Gamma delta T cells regulate the extent and duration of inflammation in the central nervous system by a Fas ligand-dependent mechanism, J. Immunol., 174, 4678, 10.4049/jimmunol.174.8.4678 Ponomarev, 2004, Gamma delta T cell regulation of IFN-gamma production by central nervous system-infiltrating encephalitogenic T cells: correlation with recovery from experimental autoimmune encephalomyelitis, J. Immunol., 173, 1587, 10.4049/jimmunol.173.3.1587 Prinz, 2006, Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis, J. Clin. Invest., 116, 456, 10.1172/JCI26078 Raivich, 2004, Brain microglia and blood-derived macrophages: molecular profiles and functional roles in multiple sclerosis and animal models of autoimmune demyelinating disease, Brain Res. Brain Res. Rev., 46, 261, 10.1016/j.brainresrev.2004.06.006 Rajan, 1996, A pathogenic role for gamma delta T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse, J. Immunol., 157, 941, 10.4049/jimmunol.157.2.941 Rajan, 1998, The effect of gammadelta T cell depletion on cytokine gene expression in experimental allergic encephalomyelitis, J. Immunol., 160, 5955, 10.4049/jimmunol.160.12.5955 Rasmussen, 2007, Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing–remitting experimental autoimmune encephalomyelitis, Brain, 130, 2816, 10.1093/brain/awm219 Rinaldi, 2006, Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients, Brain, 129, 1993, 10.1093/brain/awl179 Rinaldi, 2007, Regulatory CD56bright natural killer cells expanded during cyclophosphamide therapy in multiple sclerosis Robbie–Ryan, 2003, Cutting edge: both activating and inhibitory Fc receptors expressed on mast cells regulate experimental allergic encephalomyelitis disease severity, J. Immunol., 170, 1630, 10.4049/jimmunol.170.4.1630 Romagnani, 2005, Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells, Eur. J. Immunol., 35, 2452, 10.1002/eji.200526069 Rozniecki, 1995, Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients, Ann. Neurol., 37, 63, 10.1002/ana.410370112 Runmarker, 1993, Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up, Brain, 116, 117, 10.1093/brain/116.1.117 Saikali, 2007, NKG2D-mediated cytotoxicity toward oligodendrocytes suggests a mechanism for tissue injury in multiple sclerosis, J. Neurosci., 27, 1220, 10.1523/JNEUROSCI.4402-06.2007 Saraste, 2007, Expansion of CD56Bright natural killer cells in the peripheral blood of multiple sclerosis patients treated with interferon-beta, Neurol. Sci., 28, 121, 10.1007/s10072-007-0803-3 Secor, 2000, Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis, J. Exp. Med., 191, 813, 10.1084/jem.191.5.813 Selmaj, 1991, Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis, Proc. Natl. Acad. Sci. U. S. A., 88, 6452, 10.1073/pnas.88.15.6452 Serafini, 2000, Intracerebral recruitment and maturation of dendritic cells in the onset and progression of experimental autoimmune encephalomyelitis, Am. J. Pathol., 157, 1991, 10.1016/S0002-9440(10)64838-9 Serafini, 2008, Expression of TWEAK and its receptor Fn14 in the multiple sclerosis brain: implications for inflammatory tissue injury, J. Neuropathol. Exp. Neurol., 67, 1137, 10.1097/NEN.0b013e31818dab90 Shimonkevitz, 1993, Clonal expansions of activated gamma/delta T cells in recent-onset multiple sclerosis, Proc. Natl. Acad. Sci. U. S. A., 90, 923, 10.1073/pnas.90.3.923 Shortman, 2001, Immunity or tolerance? That is the question for dendritic cells, Nat. Immunol., 2, 988, 10.1038/ni1101-988 Siegal, 1999, The nature of the principal type 1 interferon-producing cells in human blood, Science, 284, 1835, 10.1126/science.284.5421.1835 Silver, 1996, Mast cells in the brain: evidence and functional significance, Trends Neurosci., 19, 25, 10.1016/0166-2236(96)81863-7 Singh, 2001, Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis, J. Exp. Med., 194, 1801, 10.1084/jem.194.12.1801 Sonoda, 2001, NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance, J. Immunol., 166, 42, 10.4049/jimmunol.166.1.42 Sospedra, 2005, Immunology of multiple sclerosis, Annu. Rev. Immunol., 23, 683, 10.1146/annurev.immunol.23.021704.115707 Spahn, 1999, Decreased severity of myelin oligodendrocyte glycoprotein peptide 33–35-induced experimental autoimmune encephalomyelitis in mice with a disrupted TCR delta chain gene, Eur. J. Immunol., 29, 4060, 10.1002/(SICI)1521-4141(199912)29:12<4060::AID-IMMU4060>3.0.CO;2-S Stasiolek, 2006, Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis, Brain, 129, 1293, 10.1093/brain/awl043 Stelekati, 2007, Mast cells in allergy: innate instructors of adaptive responses, Immunobiology, 212, 505, 10.1016/j.imbio.2007.03.012 Stinissen, 1995, 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, J. Immunol., 154, 4883, 10.4049/jimmunol.154.9.4883 Takahashi, 2004, The regulatory role of natural killer cells in multiple sclerosis, Brain, 127, 1917, 10.1093/brain/awh219 Takahashi, 2001, Natural killer type 2 bias in remission of multiple sclerosis, J. Clin. Invest., 107, R23, 10.1172/JCI11819 Tanzola, 2003, Mast cells exert effects outside the central nervous system to influence experimental allergic encephalomyelitis disease course, J. Immunol., 171, 4385, 10.4049/jimmunol.171.8.4385 Terness, 2008, Mitomycin C-treated dendritic cells inactivate autoreactive T cells: toward the development of a tolerogenic vaccine in autoimmune diseases, Proc. Natl. Acad. Sci. U. S. A., 105, 18442, 10.1073/pnas.0807185105 Theoharides, 1993, Synergistic action of estradiol and myelin basic protein on mast cell secretion and brain myelin changes resembling early stages of demyelination, Neuroscience, 57, 861, 10.1016/0306-4522(93)90030-J Theoharides, 2008, Human mast cells stimulate activated T cells: implications for multiple sclerosis, Ann. N. Y. Acad. Sci., 1144, 74, 10.1196/annals.1418.029 Toms, 1990, Identification of IgE-positive cells and mast cells in frozen sections of multiple sclerosis brains, J. Neuroimmunol., 30, 169, 10.1016/0165-5728(90)90101-R Traugott, 1985, Characterization and distribution of lymphocyte subpopulations in multiple sclerosis plaques versus autoimmune demyelinating lesions, Springer Semin. Immunopathol., 8, 71, 10.1007/BF00197248 Tupin, 2008, NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi, Proc. Natl. Acad. Sci. U. S. A., 105, 19863, 10.1073/pnas.0810519105 Tupin, 2006, Activation of natural killer T cells by glycolipids, Methods Enzymol., 417, 185, 10.1016/S0076-6879(06)17014-7 Tyznik, 2008, Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals, J. Immunol., 181, 4452, 10.4049/jimmunol.181.7.4452 Vaknin-Dembinsky, 2006, IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production, J. Immunol., 176, 7768, 10.4049/jimmunol.176.12.7768 Vaknin-Dembinsky, 2008, Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis, J. Neuroimmunol., 195, 140, 10.1016/j.jneuroim.2008.01.002 Vitale, 2005, NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor, Blood, 106, 566, 10.1182/blood-2004-10-4035 Vitale, 2004, The small subset of CD56brightCD16- natural killer cells is selectively responsible for both cell proliferation and interferon-gamma production upon interaction with dendritic cells, Eur. J. Immunol., 34, 1715, 10.1002/eji.200425100 Vollmer, 2005, Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen, J. Immunol., 174, 2696, 10.4049/jimmunol.174.5.2696 Walzer, 2005, Natural-killer cells and dendritic cells: “l'union fait la force”, Blood, 106, 2252, 10.1182/blood-2005-03-1154 Weiner, 2004, Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease, Arch. Neurol., 61, 1613, 10.1001/archneur.61.10.1613 Weiner, 2008, A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis, J. Neurol., 255, 3, 10.1007/s00415-008-1002-8 Weiner, 2009, The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease?, Ann. Neurol., 65, 239, 10.1002/ana.21640 Weir, 2002, Experimental autoimmune encephalomyelitis induction in naive mice by dendritic cells presenting a self-peptide, Immunol. Cell Biol., 80, 14, 10.1046/j.1440-1711.2002.01056.x Wilson, 1999, Targeting of human dendritic cells by autologous NK cells, J. Immunol., 163, 6365, 10.4049/jimmunol.163.12.6365 Winkler-Pickett, 2008, In vivo regulation of experimental autoimmune encephalomyelitis by NK cells: alteration of primary adaptive responses, J. Immunol., 180, 4495, 10.4049/jimmunol.180.7.4495 Xiao, 2004, Therapeutic potential of IFN-gamma-modified dendritic cells in acute and chronic experimental allergic encephalomyelitis, Int. Immunol., 16, 13, 10.1093/intimm/dxh003 Xu, 2005, Mechanism of natural killer (NK) cell regulatory role in experimental autoimmune encephalomyelitis, J. Neuroimmunol., 163, 24, 10.1016/j.jneuroim.2005.02.011 Zeine, 1998, Mechanism of gammadelta T cell-induced human oligodendrocyte cytotoxicity: relevance to multiple sclerosis, J. Neuroimmunol., 87, 49, 10.1016/S0165-5728(98)00047-2 Zhang, 1997, Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells, J. Exp. Med., 186, 1677, 10.1084/jem.186.10.1677 Zhang, 2002, Mature bone marrow-derived dendritic cells polarize Th2 response and suppress experimental autoimmune encephalomyelitis, Mult. Scler., 8, 463, 10.1191/1352458502ms857oa Zimmer, 2008, NK cells and Treg cells: a fascinating dance cheek to cheek, Eur. J. Immunol., 38, 2942, 10.1002/eji.200838813