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Regulation of Immune Cell Entry into the Central Nervous System

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Cell Communication in Nervous and Immune System

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 43))

Abstract

The central nervous system (CNS) has long been regarded as an immune privileged organ implying that the immune system avoids the CNS to not disturb its homeostasis, which is critical for proper function of neurons. Meanwhile, it is accepted that immune cells do in fact gain access to the CNS and that immune responses can be mounted within this tissue. However, the unique CNS microenvironment strictly controls these immune reactions starting with tightly controlling immune cell entry into the tissue. The endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid (CSF) barrier, which protect the CNS from the constantly changing milieu within the bloodstream, also strictly control immune cell entry into the CNS. Under physiological conditions, immune cell migration into the CNS is kept at a very low level. In contrast, during a variety of pathological conditions of the CNS such as viral or bacterial infections, or during inflammatory diseases such as multiple sclerosis, immunocompetent cells readily traverse the BBB and likely also the choroid plexus and subsequently enter the CNS parenchyma or CSF spaces. This chapter summarizes our current knowledge of immune cell entry across the blood CNS barriers. A large body of the currently available information on immune cell entry into the CNS has been derived from studying experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Therefore, most of this chapter discussing immune cell entry during CNS pathogenesis refers to observations in the EAE model, allowing for the possibility that other mechanisms of immune cell entry into the CNS might apply under different pathological conditions such as bacterial meningitis or stroke.

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References

  1. Adamson P, Etienne S, Couraud PO, Calder V, Greenwood J (1999) Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. J Immunol 162:2964–2973

    PubMed  CAS  Google Scholar 

  2. Allt G, Lawrenson JG (1997) Is the pial microvessel a good model for blood–brain barrier studies? Brain Res Brain Res Rev 24:67–76

    Article  PubMed  CAS  Google Scholar 

  3. Alt C, Laschinger M, Engelhardt B (2002) Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood–brain barrier suggests their possible involvement in lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis. Eur J Immunol 32:2133–2144

    Article  PubMed  CAS  Google Scholar 

  4. Andersson PB, Perry VH, Gordon S (1992a) The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues. Neuroscience 48:169–186

    Article  PubMed  CAS  Google Scholar 

  5. Andersson PB, Perry VH, Gordon S (1992b) Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system. J Exp Med 176:255–259

    Article  PubMed  CAS  Google Scholar 

  6. Archelos JJ, Jung S, Maurer M, Schmied M, Lassmann H, Tamatani T, Miyasaka M, Toyka KV, Hartung HP (1993) Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1. Ann Neurol 34:145–154

    Article  PubMed  CAS  Google Scholar 

  7. Barkalow FJ, Goodman MJ, Gerritsen ME, Mayadas TN (1996) Brain endothelium lack one of two pathways of P-selectin-mediated neutrophil adhesion. Blood 88:4585–4593

    PubMed  CAS  Google Scholar 

  8. Barker CF, Billingham RE (1977) Immunologically privileged sites. Adv Immunol 25:1–54

    Article  PubMed  CAS  Google Scholar 

  9. Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA Jr (1993) Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 177:57–68

    Article  PubMed  CAS  Google Scholar 

  10. Battistini L, Piccio L, Rossi B, Bach S, Galgani S, Gasperini C, Ottoboni L, Ciabini D, Caramia MD, Bernardi G, Laudanna C, Scarpini E, McEver RP, Butcher EC, Borsellino G, Constantin G (2003) CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1. Blood 101:4775–4782

    Article  PubMed  CAS  Google Scholar 

  11. Ben-Nun A, Wekerle H, Cohen I (1981) The rapid isolation of clonable antigen-specific T cell lines capable of mediating autoimmune encephalomyelitis. Eur J Immunol 11:195

    Article  PubMed  CAS  Google Scholar 

  12. Bixel G, Kloep S, Butz S, Petri B, Engelhardt B, Vestweber D (2004) Mouse CD99 participates in T-cell recruitment into inflamed skin. Blood 104:3205–3213

    Article  PubMed  CAS  Google Scholar 

  13. Bo L, Peterson JW, Mork S, Hoffman PA, Gallatin WM, Ransohoff RM, Trapp BD (1996) Distribution of immunoglobulin superfamily members ICAM-1, -2, -3, and the beta 2 integrin LFA-1 in multiple sclerosis lesions. J Neuropathol Exp Neurol 55:1060–1072

    PubMed  CAS  Google Scholar 

  14. Bouchaud C, Bosler O (1986) The circumventricular organs of the mammalian brain with special reference to monoaminergic innervation. Int Rev Cytol 105:283–327

    Article  PubMed  CAS  Google Scholar 

  15. Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67:1033–1036

    Article  PubMed  CAS  Google Scholar 

  16. Butcher EC, Williams M, Youngman K, Rott L, Briskin M (1999) Lymphocyte trafficking and regional immunity. Adv Immunol 72:209–253

    Article  PubMed  CAS  Google Scholar 

  17. Cannella B, Cross AH, Raine CS (1993) Anti-adhesion molecule therapy in experimental autoimmune encephalomyelitis. J Neuroimmunol 46:43–55

    Article  PubMed  CAS  Google Scholar 

  18. Cannella B, Raine CS (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 37:424–435

    Article  PubMed  CAS  Google Scholar 

  19. Carlos TM, Harlan JM (1994) Leukocyte-endothelial adhesion molecules. Blood 7:2068–2101

    Google Scholar 

  20. Carman CV, Springer TA (2004) A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol 167:377–388

    Article  PubMed  CAS  Google Scholar 

  21. Carrithers MD, Visintin I, Kang SJ, Janeway CA Jr (2000) Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment. Brain 123:1092–1101

    Article  PubMed  Google Scholar 

  22. Carvalho-Tavares J, Hickey MJ, Hutchison J, Michaud J, Sutcliffe IT, Kubes P (2000) A role for platelets and endothelial selectins in tumor necrosis factor-alpha-induced leukocyte recruitment in the brain microvasculature. Circ Res 87:1141–1148

    PubMed  CAS  Google Scholar 

  23. Cecchelli R, Dehouck B, Descamps L, Fenart L, Buee-Scherrer V, Duhem C, Lundquist S, Rentfel M, Torpier G, Dehouck MP (1999) In vitro model for evaluating drug transport across the blood-brain barrier. Adv Drug Deliver Rev 36:165–178

    Article  CAS  Google Scholar 

  24. Cinamon G, Alon R (2003) A real time in vitro assay for studying leukocyte transendothelial migration under physiological flow conditions. J Immunol Meth 273:53–62

    Article  CAS  Google Scholar 

  25. Coisne C, Dehouck L, Faveeuw C, Delplace Y, Miller F, Landry C, Morissette C, Fenart L, Cecchelli R, Tremblay P, Dehouck B (2005) Mouse syngeneic in vitro blood-brain barrier model: a new tool to examine inflammatory events in cerebral endothelium. Lab Invest 85:734–746

    Article  PubMed  CAS  Google Scholar 

  26. Columba-Cabezas S, Serafini B, Ambrosini E, Aloisi F (2003) Lymphoid chemokines CCL19 and CCL21 are expressed in the central nervous system during experimental autoimmune encephalomyelitis: implications for the maintenance of chronic neuroinflammation. Brain Pathol 13(1):38–51

    Article  PubMed  Google Scholar 

  27. Cross AH, Cannella B, Brosnan CF, Raine CS (1990) Homing to central nervous system vasculature by antigen-specific lymphocytes. I. Localization of 14C-labeled cells during acute, chronic, and relapsing experimental allergic encephalomyelitis. Lab Invest 63:162–170

    PubMed  CAS  Google Scholar 

  28. Cross AH, Raine CS (1991) Central nervous system endothelial cell-polymorphonuclear cell interactions during autoimmune demyelination. Am J Pathol 139:1401–1409

    PubMed  CAS  Google Scholar 

  29. Del Maschio A, De Luigi A, Martin-Padura I, Brockhaus M, Bartfai T, Fruscella P, Adorini L, Martino G, Furlan R, De Simoni MG, Dejana E (1999) Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J Exp Med 190:1351–1356

    Article  Google Scholar 

  30. Dzenko KA, Andjelkovic AV, Kuziel WA, Pachter JS (2001) The chemokine receptor CCR2 mediates the binding and internalization of monocyte chemoattractant protein-1 along brain microvessels. J Neurosci 21:9214–9223

    PubMed  CAS  Google Scholar 

  31. Dziegielewska KM, Ek J, Habgood MD, Saunders NR (2001) Development of the choroid plexus. Microsc Res Tech 52:5–20

    Article  PubMed  CAS  Google Scholar 

  32. Ebnet K, Suzuki A, Ohno S, Vestweber D (2004) Junctional adhesion molecules (JAMs): more molecules with dual functions? J Cell Sci 117:19–29

    Article  PubMed  CAS  Google Scholar 

  33. Elmquist JK, Scammell TE, Saper CB (1997) Mechanisms of CNS response to systemic immune challenge: the febrile response. Trends Neurosci 20:565–570

    Article  PubMed  CAS  Google Scholar 

  34. Engelhardt B (2003) Development of the blood–brain barrier. Cell Tissue Res 314:119–129

    Article  PubMed  CAS  Google Scholar 

  35. Engelhardt B, Conley FC, Kilshaw PJ, Burcher EC (1995) Lymphocytes infiltrating the CNS during inflammation display a distinctive phenotype and bind to VCAM-1 but not to MAdCAM-1. Int Immunol 7:481–491

    Article  PubMed  CAS  Google Scholar 

  36. Engelhardt B, Kempe B, Merfeld-Clauss S, Laschinger M, Furie B, Wild ML, Vestweber D (2005) PSGL-1 is not required for the development of experimental autoimmune encephalomyelitis in SJL and C57Bl6 mice. J Immunol 175:1267–1275

    PubMed  CAS  Google Scholar 

  37. Engelhardt B, Laschinger M, Schulz M, Samulowitz U, Vestweber D, Hoch G (1998) The development of experimental autoimmune encephalomyelitis in the mouse requires alpha4-integrin but not alpha4beta7-integrin. J Clin Invest 102:2096–2105

    Article  PubMed  CAS  Google Scholar 

  38. Engelhardt B, Laschinger M, Vajkoczy P (2003) Molecular mechanisms involved in lymphocyte interaction with blood-spinal cord barrier endothelium in vivo. In: Sharma HS, Westman J (eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease. Academic Press, New York, pp 19–31

    Google Scholar 

  39. Engelhardt B, Vestweber D, Hallmann R, Schulz M (1997) E- and P-selectin are not involved in the recruitment of inflammatory cells across the blood–brain barrier in experimental autoimmune encephalomyelitis. Blood 90:4459–4472

    PubMed  CAS  Google Scholar 

  40. Engelhardt B, Wolburg-Buchholz K, Wolburg H (2001) Involvement of the choroid plexus in central nervous system inflammation. Microsc Res Tech 52:112–129

    Article  PubMed  CAS  Google Scholar 

  41. Feng D, Nagy JA, Pyne K, Dvorak HF, Dvorak AM (1998) Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. J Exp Med 187:903–915

    Article  PubMed  CAS  Google Scholar 

  42. Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ (2000) CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 192:899–905

    Article  PubMed  CAS  Google Scholar 

  43. Floris S, Ruuls SR, Wierinckx A, van der Pol SM, Dopp E, van der Meide PH, Dijkstra CD, De Vries HE (2002) Interferon-beta directly influences monocyte infiltration into the central nervous system. J Neuroimmunol 127:69–79

    Article  PubMed  CAS  Google Scholar 

  44. Flugel A, Berkowicz T, Ritter T, Labeur M, Jenne DE, Li Z, Ellwart JW, Willem M, Lassmann H, Wekerle H (2001) Migratory activity and functional changes of green fluorescent effector cells before and during experimental autoimmune encephalomyelitis. Immunity 14:547–560

    Article  PubMed  CAS  Google Scholar 

  45. Glabinski AR, Ransohoff RM (1999) Chemokines and chemokine receptors in CNS pathology. J Neurovirol 5:3–12

    Article  PubMed  CAS  Google Scholar 

  46. Graesser D, Solowiej A, Bruckner M, Osterweil E, Juedes A, Davis S, Ruddle N, Engelhardt B, Madri JM (2002) Changes in vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1 (CD31) deficient mice. J Clin Invest 109:383–392

    PubMed  CAS  Google Scholar 

  47. Greenwood J, Amos CL, Walters CE, Couraud PO, Lyck R, Engelhardt B, Adamson P (2003) Intracellular domain of brain endothelial intercellular adhesion molecule-1 is essential for T lymphocyte-mediated signaling and migration. J Immunol 171:2099–2108

    PubMed  CAS  Google Scholar 

  48. Greenwood J, Howes R, Lightman S (1994) The blood–retinal barrier in experimental autoimmune uveoretinitis – leukocyte interactions and functional damage. Lab Invest 70(N1):39–52

    PubMed  CAS  Google Scholar 

  49. Greenwood J, Wang Y, Calder VL (1995) Lymphocyte adhesion and transendothelial migration in the central nervous system: the role of LFA-1, ICAM-1, VLA-4 and VCAM-1. off. Immunology 86:408–415

    PubMed  CAS  Google Scholar 

  50. 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 11:328–334

    Article  PubMed  CAS  Google Scholar 

  51. Hickey WF (1991) Migration of hematogenous cells through the blood–brain barrier and the initiation of CNS inflammation. Brain Pathol 1:97–105

    Article  PubMed  CAS  Google Scholar 

  52. Izikson L, Klein RS, Charo IF, Weiner HL, Luster AD (2000) Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J Exp Med 192:1075–1080

    Article  PubMed  CAS  Google Scholar 

  53. Johnson-Léger C, Imhof BA (2003) Forging the endothelium during inflammation: pushing at a half-open door? Cell Tiss Res 314:93–105

    Article  CAS  Google Scholar 

  54. Kallmann BA, Hummel V, Lindenlaub T, Ruprecht K, Toyka KV, Rieckmann P (2000) Cytokine-induced modulation of cellular adhesion to human cerebral endothelial cells is mediated by soluble vascular cell adhesion molecule-1. Brain 123:687–697

    Article  PubMed  Google Scholar 

  55. Kanwar JR, Harrison JE, Wang D, Leung E, Mueller W, Wagner N, Krissansen GW (2000) Beta7 integrins contribute to demyelinating disease of the central nervous system. J Neuroimmunol 103:146–152

    Article  PubMed  CAS  Google Scholar 

  56. Kent SJ, Karlik SJ, Cannon C, Hines DK, Yednock TA, Fritz LC, Horner HC (1995) A monoclonal antibody to alpha 4 integrin suppresses and reverses active experimental allergic encephalomyelitis. J Neuroimmunol 58:1–10

    Article  PubMed  CAS  Google Scholar 

  57. Kerfoot S, Kubes P (2002) Overlapping roles of P-selectin and alpha 4 integrin to recruit leukocytes to the central nervous system in experimental autoimmune encephalomyelitis. J Immunol 169:1000–1006

    PubMed  CAS  Google Scholar 

  58. Keszthelyi E, Karlik S, Hyduk S, Rice GPA, Gordon G, Yednock T, Horner H (1996) Evidence for a prolonged role of α4 integrin throughout active experimental allergic encephalomyelitis. Neurol 47:1053–1059

    CAS  Google Scholar 

  59. Kivisakk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, Wu L, Baekkevold ES, Lassmann H, Staugaitis SM, Campbell JJ, Ransohoff RM (2005) Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci USA 100:8389–8394

    Article  CAS  Google Scholar 

  60. Kniesel U, Wolburg H (2000) Tight junctions of the blood–brain barrier. Cell Mol Neurobiol 20:57–76

    Article  PubMed  CAS  Google Scholar 

  61. Laschinger M, Engelhardt B (2000) Interaction of alpha4-integrin with VCAM-1 is involved in adhesion of encephalitogenic T cell blasts to brain endothelium but not in their transendothelial migration in vitro. J Neuroimmunol 102:32–43

    Article  PubMed  CAS  Google Scholar 

  62. Laschinger M, Vajkoczy P, Engelhardt B (2002) Encephalitogenic T cells use LFA-1 during transendothelial migration but not during capture and adhesion in spinal cord microvessels in vivo. Eur J Immunol 32:3598–3606

    Article  PubMed  CAS  Google Scholar 

  63. Lassmann H (1983) Chronic relapsing experimental allergic encephalomyelitis: its value as an experimental model for multiple sclerosis. J Neurol 229:207–220

    Article  PubMed  CAS  Google Scholar 

  64. Lechner F, Sahrbacher U, Suter T, Frei K, Brockhaus M, Koedel U, Fontana A (2000) Antibodies to the junctional adhesion molecule cause disruption of endothelial cells and do not prevent leukocyte influx into the meninges after viral or bacterial infection. J Infect Dis 182:978–982

    Article  PubMed  CAS  Google Scholar 

  65. Leonhardt H (1980) Ependym und circumventriculäre Organe. In: Oksche A, Vollrath L (eds) Handbuch der mikroskopischen Anatomie des Menschen. Springer, Berlin Heidelberg New York, pp 177–666

    Google Scholar 

  66. Lossinski AS, Badmajew V, Robson J, Moretz ARC, Wisniewski HM (1989) Sites of egress of inflammatory cells and horseradish peroxidase transport across the blood–brain barrier in a murine model of chronic relapsing experimental allergic encephalomyelitis. Acta Neuropathol 78:359–371

    Article  Google Scholar 

  67. Lyck R, Reiss Y, Gerwin N, Greenwood J, Adamson P, Engelhardt B (2003) T cell interaction with ICAM-1/ICAM-2-double-deficient brain endothelium in vitro: the cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T cells. Blood 102:3675–3683

    Article  PubMed  CAS  Google Scholar 

  68. Martin R, McFarland HF (1995) Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis. Crit Rev Clin Lab Sci 32:121–182

    Article  PubMed  CAS  Google Scholar 

  69. Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD (1993) Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell 74:541–554

    Article  PubMed  CAS  Google Scholar 

  70. McMenamin PG, Forrester JV, Steptoe RJ, Dua HS (1992) Ultrastructural pathology of experimental autoimmune uveitis. Quantitative evidence of activation and possible high endothelial venule-like changes in retinal vascular endothelium. Lab Invest 67:42–55

    PubMed  CAS  Google Scholar 

  71. Medawar PB (1948) Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue and to anterior chamber of the eye. Br Exp J Pathol 29:58–69

    CAS  Google Scholar 

  72. Mempel TR, Scimone ML, Mora JR, von Andrian UH (2004) In vivo imaging of leukocyte trafficking in blood vessels and tissues. Curr Opin Immunol 16:406–417

    Article  PubMed  CAS  Google Scholar 

  73. Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348:15–23

    Article  PubMed  CAS  Google Scholar 

  74. Muller WA (2003) Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol 6:327–334

    Google Scholar 

  75. O'Neill JK, Butter C, Baker D, Gschmeissner SE, Kraal G, Butcher EC, Turk JL (1991) Expression of vascular addressins and ICAM-1 by endothelial cells in the spinal cord during chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse. Immunology 72:520–525

    PubMed  Google Scholar 

  76. Osmers I, Bullard DC, Barnum SR (2005) PSGL-1 is not required for development of experimental autoimmune encephalomyelitis. J Neuroimmunol 166:193–196

    Article  PubMed  CAS  Google Scholar 

  77. Piccio L, Rossi B, Colantonio L, Grenningloh R, Gho A, Ottoboni L, Homeister JW, Scarpini E, Martinello M, Laudanna C, D'Ambrosio D, Lowe JB, Constantin G (2005) Efficient recruitment of lymphocytes in inflamed brain venules requires expression of cutaneous lymphocyte antigen and fucosyltransferase-VII. J Immunol 174:5805–5813

    PubMed  CAS  Google Scholar 

  78. Piccio L, Rossi B, Scarpini E, Laudanna C, Giagulli C, Issekutz AC, Vestweber D, Butcher EC, Constantin G (2002) Molecular mechanisms involved in lymphocyte recruitment in inflamed brain microvessels: critical roles for P-selectin glycoprotein ligand-1 and heterotrimeric G(i)-linked receptors. J Immunol 168:1940–1949

    PubMed  CAS  Google Scholar 

  79. Qing Z, Sandor M, Radvany Z, Sewell D, Falus A, Potthoff D, Muller WA, Fabry Z (2001) Inhibition of antigen-specific T cell trafficking into the central nervous system via blocking PECAM1/CD31 molecule. J Neuropathol Exp Neurol 60:798–807

    PubMed  CAS  Google Scholar 

  80. Raine CS, Cannella B, Duijvestijn AM, Cross AH (1990) Homing to central nervous system vasculature by antigen-specific lymphocytes. ILymphocyte I/endothelial cell adhesion during the initial stages of autoimmune demyelination. Lab Invest 63:476–489

    PubMed  CAS  Google Scholar 

  81. Ransohoff RM (2002) The chemokine system in neuroinflammation: an update. J Infect Dis 186 Suppl 2:S152–S156

    Google Scholar 

  82. Rascher G, Wolburg H (1997) The tight junctions of the leptomeningeal blood-cerebrospinal fluid barrier during development. J Hirnforsch 38:525–540

    PubMed  CAS  Google Scholar 

  83. Reiss Y, Hoch G, Deutsch U, Engelhardt B (1998) T cell interaction with ICAM-1-deficient endothelium in vitro: essential role for ICAM-1 and ICAM-2 in transendothelial migration of T cells. Eur J Immunol 28:3086–3099

    Article  PubMed  CAS  Google Scholar 

  84. Rot A, von Andrian UH (2004) Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol 22:891–928

    Article  PubMed  CAS  Google Scholar 

  85. Rubin LL, Hall DE, Porter S, Barbu K, Cannon C, Horner HC, Janatpour M, Liaw CW, Manning K, Morales J, Tanner LI, Tomaselli KJ et al. (1991) A cell-culture model of the blood–brain barrier. J Cell Biol 115:1725–1735

    Article  PubMed  CAS  Google Scholar 

  86. Ryan G, Grimes T, Brankin B, Mabruk MJ, Hosie MJ, Jarrett O, Callanan JJ (2005) Neuropathology associated with feline immunodeficiency virus infection highlights prominent lymphocyte trafficking through both the blood-brain and blood-choroid plexus barriers. J Neurovirol 11:337–345

    Article  PubMed  CAS  Google Scholar 

  87. Schenkel AR, Mamdouh Z, Chen X, Liebman RM, Muller WA (2002) CD99 plays a major role in the migration of monocytes through endothelial junctions. Nat Immunol 3:143–150

    Article  PubMed  CAS  Google Scholar 

  88. Schulz M, Engelhardt B (2005) The circumventricular organs participate in the immunopathogenesis of experimental autoimmune encephalomyelitis. Cerebrospinal Fluid Res

    Google Scholar 

  89. Seguin R, Biernacki K, Rotondo RL, Prat A, Antel JP (2003) Regulation and functional effects of monocyte migration across human brain-derived endothelial cells. J Neuropathol Exp Neurol 62:412–419

    PubMed  CAS  Google Scholar 

  90. Sobel RA, Mitchell ME, Fondren G (1990) Intercellular Adhesion Molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 136:1309–1316

    PubMed  CAS  Google Scholar 

  91. Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747

    Article  PubMed  CAS  Google Scholar 

  92. Springer TA (1990) Adhesion receptors of the immune system. Nature 346:425–434

    Article  PubMed  CAS  Google Scholar 

  93. Springer TA, Wang JH (2004) The three-dimensional structure of integrins and their ligands, and conformational regulation of cell adhesion. Adv Protein Chem 68:29–63

    Article  PubMed  CAS  Google Scholar 

  94. Steffen BJ, Breier G, Butcher EC, Schulz M, Engelhardt B (1996) ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro. Am J Pathol 148:1819–1838

    PubMed  CAS  Google Scholar 

  95. Steffen BJ, Butcher EC, Engelhardt B (1994) Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in the SJL/J mouse. Am Pathol J 145(N1):189–201

    CAS  Google Scholar 

  96. Sumen C, Mempel TR, Mazo IB, von Andrian UH (2004) Intravital microscopy: visualizing immunity in context. Immunity 21:315–329

    PubMed  CAS  Google Scholar 

  97. Theien BE, Vanderlugt CL, Nickerson-Nutter C, Cornebise M, Scott DM, Perper SJ, Whalley ET, Miller SD (2003) Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE. Blood 102:4464–4471

    Article  PubMed  CAS  Google Scholar 

  98. Vajkoczy P, Laschinger M, Engelhardt B (2001) Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J Clin Invest 108:557–565

    PubMed  CAS  Google Scholar 

  99. Wekerle H, Engelhardt B, Risau W, Meyermann R (1991) Interaction of T lymphocytes with cerebral endothelial cells in vitro. Brain Pathol 1:107–114

    Article  PubMed  CAS  Google Scholar 

  100. Wekerle H, Kojima K, Lannes-Vieira J, Lassmann H, Linington C (1994) Animal models. Ann Neurol 36:S47–S53

    Article  PubMed  CAS  Google Scholar 

  101. Wekerle H, Linington C, Lassmann H, Meyermann R (1986) Cellular immune reactivity within the CNS. TINS 9:271–277

    Google Scholar 

  102. Welsh CT, Rose JW, Hill KE, Townsend JJ (1993) Augmentation of adoptively transferred experimental allergic encephalomyelitis by administration of a monoclonal antibody specific for LFA-1α. J Neuroimmunol 43:161–168

    Article  PubMed  CAS  Google Scholar 

  103. Willenborg DO, Simmons RD, Tamatani T, Miyasaka M (1993) ICAM-1-dependent pathway is not critically involved in the inflammatory process of autoimmune encephalomyelitis or in cytokine-induced inflammation of the central nervous system. J Neuroimmunol 45:147–154

    Article  PubMed  CAS  Google Scholar 

  104. Wolburg H, Neuhaus J, Kniesel U, Krauss B, Schmid EM, Ocalan M, Farrell C, Risau W (1994) Modulation of tight junction structure in blood-brain-barrier endothelial-cells—effects of tissue-culture, 2nd messengers and cocultured astrocytes. Cell J Sci 107(MAY):1347–1357

    Google Scholar 

  105. Wolburg H, Wolburg-Buchholz K, Engelhardt B (2005) Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol 109:181–190

    Article  PubMed  Google Scholar 

  106. Wong D, Prameya R, Dorovini-Zis K (1999) In vitro adhesion and migration of T lymphocytes across monolayers of human brain microvessel endothelial cells: regulation by ICAM-1, VCAM-1, E-Selectin and PECAM-1. Neuropathol J Exp Neurol 58:138

    Article  CAS  Google Scholar 

  107. Yednock TA, Cannon C, Fritz LC, Sanchez Madrid F, Steinman L, Karin N (1992a) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356:63–66

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Britta Engelhardt .

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Eckart D. Gundelfinger Constanze I. Seidenbecher Burkhart Schraven

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© 2006 Springer-Verlag Berlin Heidelberg

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Engelhardt, B. (2006). Regulation of Immune Cell Entry into the Central Nervous System. In: Gundelfinger, E.D., Seidenbecher, C.I., Schraven, B. (eds) Cell Communication in Nervous and Immune System. Results and Problems in Cell Differentiation, vol 43. Springer, Berlin, Heidelberg . https://doi.org/10.1007/400_020

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