Functional Diversity of Chemokines and Chemokine Receptors in Response to Viral Infection of the Central Nervous System

  • T. E. Lane
  • J. L. Hardison
  • K. B. Walsh
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 303)


Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS.


Experimental Autoimmune Encephalomyelitis Chemokine Receptor Severe Acute Respiratory Syndrome Mouse Hepatitis Virus Severe Acute Respiratory Syndrome Coronavirus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Baggiolini M (2001) Chemokines in pathology and medicine. J Intern Med 250:91–104PubMedCrossRefGoogle Scholar
  2. 2.
    Balashov KE, Rottman JB, Weiner HL, Hancock WW (1999) CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. Proc Natl Acad Sci U S A 96:6873–6878PubMedCrossRefGoogle Scholar
  3. 3.
    Banisor I, Leist TP, Kalman B (2005) Involvement of beta-chemokines in the development of inflammatory demyelination. J Neuroinflammation 2:7PubMedCrossRefGoogle Scholar
  4. 4.
    Bartosik-Psujek H, Stelmasiak Z (2005) The levels of chemokines CXCL8, CCL2 and CCL5 in multiple sclerosis patients are linked to the activity of the disease. Eur J Neurol 12:49–54PubMedCrossRefGoogle Scholar
  5. 5.
    Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997) A new class of membrane-bound chemokine with a CX3C motif. Nature 385:640–644PubMedCrossRefGoogle Scholar
  6. 6.
    Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP (1999) Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220PubMedCrossRefGoogle Scholar
  7. 7.
    Boring L, Gosling J, Monteclaro FS, Lusis AJ, Tsou CL, Charo IF (1996) Molecular cloning and functional expression of murine JE (monocyte chemoattractant protein 1) and murine macrophage inflammatory protein 1alpha receptors: evidence for two closely linked C-C chemokine receptors on chromosome 9. J Biol Chem 271:7551–7558PubMedCrossRefGoogle Scholar
  8. 8.
    Boring L, Gosling J, Cleary M, Charo IF (1998) Decreased lesion formation in —/—CCR2—/—mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394:894–897PubMedCrossRefGoogle Scholar
  9. 9.
    Buchmeier MJ, Lewicki HA, Talbot PJ, Knobler RL (1984) Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology 132:261–270PubMedCrossRefGoogle Scholar
  10. 10.
    Cartier L, Hartley O, Dubois-Dauphin M, Krause KH (2005) Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48:16–42PubMedCrossRefGoogle Scholar
  11. 11.
    Castro RF, Perlman S (1995) CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity. J Virol 69:8127–8131PubMedGoogle Scholar
  12. 12.
    Cheever FS, Daniels JB, Pappenheimer AM, Bailey OT (1949) A murine virus (JHM) causing disseminated encephalomyelitis with extensive destruction of myelin. J Exp Med 90:181–194CrossRefPubMedGoogle Scholar
  13. 13.
    Chen BP, Kuziel WA, Lane TE (2001) Lack of CCR2 results in increased mortality and impaired leukocyte activation and trafficking following infection of the central nervous system with a neurotropic coronavirus. J Immunol 167:4585–4592PubMedGoogle Scholar
  14. 14.
    Clark-Lewis I, Kim KS, Rajarathnam K, Gong JH, Dewald B, Moser B, Baggiolini M, Sykes BD (1995) Structure-activity relationships of chemokines. J Leukoc Biol 57:703–711PubMedGoogle Scholar
  15. 15.
    Cook DN, Beck MA, Coffman TM, Kirby SL, Sheridan JF, Pragnell IB, Smithies O (1995) Requirement of MIP-1 alpha for an inflammatory response to viral infection. Science 269:1583–1585PubMedCrossRefGoogle Scholar
  16. 16.
    Dandekar AA, Perlman S (2002) Virus-induced demyelination in nude mice is mediated by gamma delta T cells. Am J Pathol 161:1255–1263PubMedGoogle Scholar
  17. 17.
    Domachowske JB, Bonville CA, Gao JL, Murphy PM, Easton AJ, Rosenberg HF (2000) The chemokine macrophage-inflammatory protein-1 alpha and its receptor CCR1 control pulmonary inflammation and antiviral host defense in paramyxovirus infection. J Immunol 165:2677–2682PubMedGoogle Scholar
  18. 18.
    Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD (2002) IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168:3195–3204PubMedGoogle Scholar
  19. 19.
    Farber JM (1997) Mig and IP-10: CXC chemokines that target lymphocytes. J Leukoc Biol 61:246–257PubMedGoogle Scholar
  20. 20.
    Fife BT, Kennedy KJ, Paniagua MC, Lukacs NW, Kunkel SL, Luster AD, Karpus WJ (2001) CXCL10 (IFN-gamma-inducible protein-10) control of encephalitogenic CD4+ T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol 166:7617–7624PubMedGoogle Scholar
  21. 21.
    Fischer FR, Luo Y, Luo M, Santambrogio L, Dorf ME (2001) RANTES-induced chemokine cascade in dendritic cells. J Immunol 167:1637–1643PubMedGoogle Scholar
  22. 22.
    Fischer HG, Bonifas U, Reichmann G (2000) Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii. J Immunol 164:4826–4834PubMedGoogle Scholar
  23. 23.
    Fischer HG, Reichmann G (2001) Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol 166:2717–2726PubMedGoogle Scholar
  24. 24.
    Flesch IE, Stober D, Schirmbeck R, Reimann J (2000) Monocyte inflammatory protein-1 alpha facilitates priming of CD8(+) T cell responses to exogenous viral antigen. Int Immunol 12:1365–1370PubMedCrossRefGoogle Scholar
  25. 25.
    Franciotta D, Martino G, Zardini E, Furlan R, Bergamaschi R, Andreoni L, Cosi V (2001) Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies. J Neuroimmunol 115:192–198PubMedCrossRefGoogle Scholar
  26. 26.
    Gade-Andavolu R, Comings DE, MacMurray J, Vuthoori RK, Tourtellotte WW, Nagra RM, Cone LA (2004) RANTES: a genetic risk marker for multiple sclerosis. Mult Scler 10:536–539PubMedCrossRefGoogle Scholar
  27. 27.
    Galimberti D, Bresolin N, Scarpini E (2004) Chemokine network in multiple sclerosis: role in pathogenesis and targeting for future treatments. Expert Rev Neurother 4:439–453PubMedCrossRefGoogle Scholar
  28. 28.
    Gerard C, Rollins BJ (2001) Chemokines and disease. Nat Immunol 2:108–115PubMedCrossRefGoogle Scholar
  29. 29.
    Glass WG, Liu MT, Kuziel WA, Lane TE (2001) Reduced macrophage infiltration and demyelination in mice lacking the chemokine receptor CCR5 following infection with a neurotropic coronavirus. Virology 288:8–17PubMedCrossRefGoogle Scholar
  30. 30.
    Glass WG, Lane TE (2003) Functional analysis of the CC chemokine receptor 5 (CCR5) on virus-specific CD8+ T cells following coronavirus infection of the central nervous system. Virology 312:407–414PubMedCrossRefGoogle Scholar
  31. 31.
    Glass WG, Lane TE (2003) Functional expression of chemokine receptor CCR5 on CD4(+) T cells during virus-induced central nervous system disease. J Virol 77:191–198PubMedCrossRefGoogle Scholar
  32. 32.
    Glass WG, Hickey MJ, Hardison JL, Liu MT, Manning JE, Lane TE (2004) Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis. J Immunol 172:4018–4025PubMedGoogle Scholar
  33. 33.
    Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, Young SG, Rollins BJ, Charo IF (1999) MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 103:773–778PubMedGoogle Scholar
  34. 34.
    Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11:328–334PubMedCrossRefGoogle Scholar
  35. 35.
    Gu L, Tseng SC, Rollins BJ (1999) Monocyte chemoattractant protein-1. Chem Immunol 72:7–29PubMedGoogle Scholar
  36. 36.
    Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ (2000) Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404:407–411PubMedCrossRefGoogle Scholar
  37. 37.
    Haring JS, Pewe LL, Perlman S (2001) High-magnitude, virus-specific CD4 T-cell response in the central nervous system of coronavirus-infected mice. J Virol 75:3043–3047PubMedCrossRefGoogle Scholar
  38. 38.
    Haring JS, Perlman S (2003) Bystander CD4 T cells do not mediate demyelination in mice infected with a neurotropic coronavirus. J Neuroimmunol 137:42–50PubMedCrossRefGoogle Scholar
  39. 39.
    Held KS, Chen BP, Kuziel WA, Rollins BJ, Lane TE (2004) Differential roles of CCL2 and CCR2 in host defense to coronavirus infection. Virology 329:251–260PubMedGoogle Scholar
  40. 40.
    Hildebrandt GC, Corrion LA, Olkiewicz KM, Lu B, Lowler K, Duffner UA, Moore BB, Kuziel WA, Liu C, Cooke KR (2004) Blockade of CXCR3 receptor: ligand interactions reduces leukocyte recruitment to the lung and the severity of experimental idiopathic pneumonia syndrome. J Immunol 173:2050–2059PubMedGoogle Scholar
  41. 41.
    Hogaboam CM, Lukacs NW, Chensue SW, Strieter RM, Kunkel SL (1998) Monocyte chemoattractant protein-1 synthesis by murine lung fibroblasts modulates CD4+ T cell activation. J Immunol 160:4606–4614PubMedGoogle Scholar
  42. 42.
    Holmes K, Lai M (1996) Coronaviridae: the viruses and their replication. In: Fields BN, Knipe DM, Howley PM (eds) Fields virology. Lippincott-Raven Publishers, New York, pp 1075–1094Google Scholar
  43. 43.
    Holmes KV (2003) SARS-associated coronavirus. N Engl J Med 348:1948–1951PubMedCrossRefGoogle Scholar
  44. 44.
    Houck JC, Chang CM (1977) The purification and characterization of a lymphokine chemotactic for lymphocytes—lymphotactin. Inflammation 2:105–113PubMedCrossRefGoogle Scholar
  45. 45.
    Huffnagle GB, McNeil LK, McDonald RA, Murphy JW, Toews GB, Maeda N, Kuziel WA (1999) Cutting edge: role of C-C chemokine receptor 5 in organ-specific and innate immunity to Cryptococcus neoformans. J Immunol 163:4642–4646PubMedGoogle Scholar
  46. 46.
    Karpus WJ, Lukacs NW, Kennedy KJ, Smith WS, Hurst SD, Barrett TA (1997) Differential CC chemokine-induced enhancement of T helper cell cytokine production. J Immunol 158:4129–4136PubMedGoogle Scholar
  47. 47.
    Kim TS, Perlman S (2005) Viral expression of CCL2 is sufficient to induce demyelination in —/—RAG1—/—mice infected with a neurotropic coronavirus. J Virol 79:7113–7120PubMedCrossRefGoogle Scholar
  48. 48.
    Kim TS, Perlman S (2005) Virus-specific antibody, in the absence of T cells, mediates demyelination in mice infected with a neurotropic coronavirus. Am J Pathol 166:801–809PubMedGoogle Scholar
  49. 49.
    Klein RS, Izikson L, Means T, Gibson HD, Lin E, Sobel RA, Weiner HL, Luster AD (2004) IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of experimental autoimmune encephalomyelitis. J Immunol 172:550–559PubMedGoogle Scholar
  50. 50.
    Lai MM, Cavanagh D (1997) The molecular biology of coronaviruses. Adv Virus Res 48:1–100PubMedCrossRefGoogle Scholar
  51. 51.
    Lane TE, Buchmeier MJ (1997) Murine coronavirus infection: a paradigm for virus-induced demyelinating disease. Trends Microbiol 5:9–14PubMedCrossRefGoogle Scholar
  52. 52.
    Lane TE, Asensio VC, Yu N, Paoletti AD, Campbell IL, Buchmeier MJ (1998) Dynamic regulation of alpha-and beta-chemokine expression in the central nervous system during mouse hepatitis virus-induced demyelinating disease. J Immunol 160:970–978PubMedGoogle Scholar
  53. 53.
    Lane TE, Liu MT, Chen BP, Asensio VC, Samawi RM, Paoletti AD, Campbell IL, Kunkel SL, Fox HS, Buchmeier MJ (2000) A central role for CD4(+) T cells and RANTES in virus-induced central nervous system inflammation and demyelination. J Virol 74:1415–1424PubMedCrossRefGoogle Scholar
  54. 54.
    Lazzeri E, Romagnani P (2005) CXCR3-binding chemokines: novel multifunctional therapeutic targets. Curr Drug Targets Immune Endocr Metabol Disord 5:109–118PubMedCrossRefGoogle Scholar
  55. 55.
    Lin MT, Stohlman SA, Hinton DR (1997) Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis. J Virol 71:383–391PubMedGoogle Scholar
  56. 56.
    Lin MT, Hinton DR, Marten NW, Bergmann CC, Stohlman SA (1999) Antibody prevents virus reactivation within the central nervous system. J Immunol 162:7358–7368PubMedGoogle Scholar
  57. 57.
    Liu MT, Chen BP, Oertel P, Buchmeier MJ, Armstrong D, Hamilton TA, Lane TE (2000) The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease. J Immunol 165:2327–2330PubMedGoogle Scholar
  58. 58.
    Liu MT, Armstrong D, Hamilton TA, Lane TE (2001) Expression of Mig (monokine induced by interferon-gamma) is important in T lymphocyte recruitment and host defense following viral infection of the central nervous system. J Immunol 166:1790–1795PubMedGoogle Scholar
  59. 59.
    Liu MT, Keirstead HS, Lane TE (2001) Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurological function in a viral model of multiple sclerosis. J Immunol 167:4091–4097PubMedGoogle Scholar
  60. 60.
    Luster AD (1998) Chemokines—chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445PubMedCrossRefGoogle Scholar
  61. 61.
    Mahad DJ, Ransohoff RM (2003) The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Semin Immunol 15:23–32PubMedCrossRefGoogle Scholar
  62. 62.
    Marten NW, Stohlman SA, Bergmann CC (2000) Role of viral persistence in retaining CD8(+) T cells within the central nervous system. J Virol 74:7903–7910PubMedCrossRefGoogle Scholar
  63. 63.
    Matsui M, Araya SI, Wang HY, Matsushima K, Saida T (2005) Differences in systemic and central nervous system cellular immunity relevant to relapsing-remitting multiple sclerosis. J Neurol 252:908–915PubMedCrossRefGoogle Scholar
  64. 64.
    McIntosh K (1996) Diagnostic virology. In: Fields BN, Knipe DM, Howley PM (eds) Fields virology. Lippincott-Raven Publishers, New York, pp 401–430Google Scholar
  65. 65.
    McMahon EJ, Bailey SL, Castenada CV, Waldner H, Miller SD (2005) Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med 11:335–339PubMedCrossRefGoogle Scholar
  66. 66.
    Megjugorac NJ, Young HA, Amrute SB, Olshalsky SL, Fitzgerald-Bocarsly P (2004) Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells. J Leukoc Biol 75:504–514PubMedCrossRefGoogle Scholar
  67. 67.
    Mehrad B, Moore TA, Standiford TJ (2000) Macrophage inflammatory protein-1 alpha is a critical mediator of host defense against invasive pulmonary aspergillosis in neutropenic hosts. J Immunol 165:962–968PubMedGoogle Scholar
  68. 68.
    Meyer A, Coyle AJ, Proudfoot AE, Wells TN, Power CA (1996) Cloning and characterization of a novel murine macrophage inflammatory protein-1 alpha receptor. J Biol Chem 271:14445–14451PubMedCrossRefGoogle Scholar
  69. 69.
    Miller SD, Vanderlugt CL, Begolka WS, Pao W, Yauch RL, Neville KL, Katz-Levy Y, Carrizosa A, Kim BS (1997) Persistent infection with Theiler’s virus leads to CNS autoimmunity via epitope spreading. Nat Med 3:1133–1136PubMedCrossRefGoogle Scholar
  70. 70.
    Muller DM, Pender MP, Greer JM (2004) Chemokines and chemokine receptors: potential therapeutic targets in multiple sclerosis. Curr Drug Targets Inflamm Allergy 3:279–290PubMedCrossRefGoogle Scholar
  71. 71.
    Narumi S, Kaburaki T, Yoneyama H, Iwamura H, Kobayashi Y, Matsushima K (2002) Neutralization of IFN-inducible protein 10/CXCL10 exacerbates experimental autoimmune encephalomyelitis. Eur J Immunol 32:1784–1791PubMedCrossRefGoogle Scholar
  72. 72.
    Olszewski MA, Huffnagle GB, McDonald RA, Lindell DM, Moore BB, Cook DN, Toews GB (2000) The role of macrophage inflammatory protein-1 alpha/CCL3 in regulation of T cell-mediated immunity to Cryptococcus neoformans infection. J Immunol 165:6429–6436PubMedGoogle Scholar
  73. 73.
    Parra B, Hinton DR, Marten NW, Bergmann CC, Lin MT, Yang CS, Stohlman SA (1999) IFN-gamma is required for viral clearance from central nervous system oligodendroglia. J Immunol 162:1641–1647PubMedGoogle Scholar
  74. 74.
    Parra B, Lin MT, Stohlman SA, Bergmann CC, Atkinson R, Hinton DR (2000) Contributions of Fas-Fas ligand interactions to the pathogenesis of mouse hepatitis virus in the central nervous system. J Virol 74:2447–2450PubMedCrossRefGoogle Scholar
  75. 75.
    Patterson CE, Daley JK, Echols LA, Lane TE, Rall GF (2003)Measles virus infection induces chemokine synthesis by neurons. J Immunol 171:3102–3109PubMedGoogle Scholar
  76. 76.
    Pearce BD, Hobbs MV, McGraw TS, Buchmeier MJ (1994) Cytokine induction during T-cell-mediated clearance of mouse hepatitis virus from neurons in vivo. J Virol 68:5483–5495PubMedGoogle Scholar
  77. 77.
    Penna G, Vulcano M, Roncari A, Facchetti F, Sozzani S, Adorini L (2002) Cutting edge: differential chemokine production by myeloid and plasmacytoid dendritic cells. J Immunol 169:6673–6676PubMedGoogle Scholar
  78. 78.
    Penna G, Vulcano M, Sozzani S, Adorini L (2002) Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells. Hum Immunol 63:1164–1171PubMedCrossRefGoogle Scholar
  79. 79.
    Perlman SR, Lane TE, Buchmeier MJ (1999) Coronaviruses: hepatitis, peritonitis and central nervous system disease. In: Cunningham MW, Fujinami RS (eds) Effects of microbes on the immune system, vol. 1. Lippincott Williams and Wilkins, Philadelphia, pp 331–348Google Scholar
  80. 80.
    Pewe L, Haring J, Perlman S (2002) CD4 T-cell-mediated demyelination is increased in the absence of gamma interferon in mice infected with mouse hepatitis virus. J Virol 76:7329–7333PubMedCrossRefGoogle Scholar
  81. 81.
    Pewe L, Perlman S (2002) Cutting edge: CD8Tcell-mediated demyelination is IFN-gamma dependent in mice infected with a neurotropic coronavirus. J Immunol 168:1547–1551PubMedGoogle Scholar
  82. 82.
    Phillips JJ, Chua M, Seo SH, Weiss SR (2001) Multiple regions of the murine coronavirus spike glycoprotein influence neurovirulence. J Neurovirol 7:421–431PubMedCrossRefGoogle Scholar
  83. 83.
    Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, Koch AE, Moser B, Mackay CR (1998) The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 101:746–754PubMedCrossRefGoogle Scholar
  84. 84.
    Ramakrishna C, Stohlman SA, Atkinson RD, Shlomchik MJ, Bergmann CC (2002) Mechanisms of central nervous system viral persistence: the critical role of antibody and B cells. J Immunol 168:1204–1211PubMedGoogle Scholar
  85. 85.
    Ramakrishna C, Bergmann CC, Atkinson R, Stohlman SA (2003) Control of central nervous system viral persistence by neutralizing antibody. J Virol 77:4670–4678PubMedCrossRefGoogle Scholar
  86. 86.
    Raport CJ, Gosling J, Schweickart VL, Gray PW, Charo IF (1996) Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. J Biol Chem 271:17161–17166PubMedCrossRefGoogle Scholar
  87. 87.
    Salomon I, Netzer N, Wildbaum G, Schif-Zuck S, Maor G, Karin N (2002) Targeting the function of IFN-gamma-inducible protein 10 suppresses ongoing adjuvant arthritis. J Immunol 169:2685–2693PubMedGoogle Scholar
  88. 88.
    Sato N, Kuziel WA, Melby PC, Reddick RL, Kostecki V, Zhao W, Maeda N, Ahuja SK, Ahuja SS (1999) Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. J Immunol 163:5519–5525PubMedGoogle Scholar
  89. 89.
    Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM, Frederiksen JL, Ransohoff RM (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 103:807–815PubMedGoogle Scholar
  90. 90.
    Sorensen TL, Trebst C, Kivisakk P, Klaege KL, Majmudar A, Ravid R, Lassmann H, Olsen DB, Strieter RM, Ransohoff RM, Sellebjerg F (2002) Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system. J Neuroimmunol 127:59–68PubMedCrossRefGoogle Scholar
  91. 91.
    Stamatovic SM, Shakui P, Keep RF, Moore BB, Kunkel SL, Van Rooijen N, Andjelkovic AV (2005) Monocyte chemoattractant protein-1 regulationof blood-brain barrier permeability. J Cereb Blood Flow Metab 25:593–606PubMedCrossRefGoogle Scholar
  92. 92.
    Stohlman SA, Bergmann CC, Lin MT, Cua DJ, Hinton DR (1998) CTL effector function within the central nervous system requires CD4+ T cells. J Immunol 160:2896–2904PubMedGoogle Scholar
  93. 93.
    Stohlman SA, Ramakrishna C, Tschen SI, Hinton DR, Bergmann CC (2002) The art of survival during viral persistence. J Neurovirol 8[Suppl 2]:53–58PubMedCrossRefGoogle Scholar
  94. 94.
    Taub DD, Oppenheim JJ (1994) Chemokines, inflammation and the immune system. Ther Immunol 1:229–246PubMedGoogle Scholar
  95. 95.
    Trifilo MJ, Bergmann CC, Kuziel WA, Lane TE (2003) CC chemokine ligand 3 (CCL3) regulates CD8(+)-T-cell effector function and migration following viral infection. J Virol 77:4004–4014PubMedCrossRefGoogle Scholar
  96. 96.
    Trifilo MJ, Lane TE (2004) The CC chemokine ligand 3 regulates CD11c+CD11b+ CD8alpha-dendritic cell maturation and activation following viral infection of the central nervous system: implications for a role in T cell activation. Virology 327:8–15PubMedCrossRefGoogle Scholar
  97. 97.
    Trifilo MJ, Montalto-Morrison C, Stiles LN, Hurst KR, Hardison JL, Manning JE, Masters PS, Lane TE (2004) CXC chemokine ligand 10 controls viral infection in the central nervous system: evidence for a role in innate immune response through recruitment and activation of natural killer cells. J Virol 78:585–594PubMedCrossRefGoogle Scholar
  98. 98.
    Tsunoda I, Lane TE, Blackett J, Fujinami RS (2004) Distinct roles for IP-10/CXCL10 in three animal models, Theiler’s virus infection, EAE, and MHV infection, for multiple sclerosis: implication of differing roles for IP-10. Mult Scler 10:26–34PubMedCrossRefGoogle Scholar
  99. 99.
    Warmington KS, Boring L, Ruth JH, Sonstein J, Hogaboam CM, Curtis JL, Kunkel SL, Charo IR, Chensue SW (1999) Effect of C-C chemokine receptor 2 (CCR2) knockout on type-2 (schistosomal antigen-elicited) pulmonary granuloma formation: analysis of cellular recruitment and cytokine responses. Am J Pathol 154:1407–1416PubMedGoogle Scholar
  100. 100.
    Watanabe R, Wege H, ter Meulen V (1983) Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitis. Nature 305:150–153PubMedCrossRefGoogle Scholar
  101. 101.
    Whiting D, Hsieh G, Yun JJ, Banerji A, Yao W, Fishbein MC, Belperio J, Strieter RM, Bonavida B, Ardehali A (2004) Chemokine monokine induced by IFN-gamma/CXC chemokine ligand 9 stimulates T lymphocyte proliferation and effector cytokine production. J Immunol 172:7417–7424PubMedGoogle Scholar
  102. 102.
    Widney DP, Hu Y, Foreman-Wykert AK, Bui KC, Nguyen TT, Lu B, Gerard C, Miller JF, Smith JB (2005) CXCR3 and its ligands participate in the host response to Bordetella bronchiseptica infection of the mouse respiratory tract but are not required for clearance of bacteria from the lung. Infect Immun 73:485–493PubMedCrossRefGoogle Scholar
  103. 103.
    Williamson JS, Stohlman SA (1990) Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells. J Virol 64:4589–4592PubMedGoogle Scholar
  104. 104.
    Williamson JS, Sykes KC, Stohlman SA (1991) Characterization of brain-infiltrating mononuclear cells during infection with mouse hepatitis virus strain JHM. J Neuroimmunol 32:199–207PubMedCrossRefGoogle Scholar
  105. 105.
    Wu GF, Dandekar AA, Pewe L, Perlman S (2000) CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination. J Immunol 165:2278–2286PubMedGoogle Scholar
  106. 106.
    Xie JH, Nomura N, Lu M, Chen SL, Koch GE, Weng Y, Rosa R, Di Salvo J, Mudgett J, Peterson LB, Wicker LS, DeMartino JA (2003) Antibody-mediated blockade of the CXCR3 chemokine receptor results in diminished recruitment of T helper 1 cells into sites of inflammation. J Leukoc Biol 73:771–780PubMedCrossRefGoogle Scholar
  107. 107.
    Xue S, Jaszewski A, Perlman S (1995) Identification of a CD4+ T cell epitope within the M protein of a neurotropic coronavirus. Virology 208:173–179PubMedCrossRefGoogle Scholar
  108. 108.
    Zhang Y, Yoneyama H, Wang Y, Ishikawa S, Hashimoto S, Gao JL, Murphy P, Matsushima K (2004) Mobilization of dendritic cell precursors into the circulation by administration of MIP-1alpha in mice. J Natl Cancer Inst 96:201–209PubMedGoogle Scholar
  109. 109.
    Zhou Y, Kurihara T, Ryseck RP, Yang Y, Ryan C, Loy J, Warr G, Bravo R (1998) Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor. J Immunol 160:4018–4025PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • T. E. Lane
    • 1
  • J. L. Hardison
    • 1
  • K. B. Walsh
    • 1
  1. 1.Department of Molecular Biology and BiochemistryUniversity of CaliforniaIrvineUSA

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