Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 166

The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.

Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes

Open access
Laman, Jon D., Weller, Roy O.·2013·Journal of Neuroimmune Pharmacology
DOI 10.1007/s11481-013-9470-8
Open this paper in CoChat — free account

Abstract

Despite the absence of conventional lymphatics, there is efficient drainage of both cerebrospinal fluid (CSF) and interstitial fluid (ISF) from the CNS to regional lymph nodes. CSF drains from the subarachnoid space by channels that pass through the cribriform plate of the ethmoid bone to the nasal mucosa and cervical lymph nodes in animals and in humans; antigen presenting cells (APC) migrate along this pathway to lymph nodes. ISF and solutes drain from the brain parenchyma to cervical lymph nodes by a separate route along 100–150 nm wide basement membranes in the walls of cerebral capillaries and arteries. This pathway is too narrow for the migration of APC so it is unlikely that APC traffic directly from brain parenchyma to lymph nodes by this route. We present a model for the pivotal involvement of regional lymph nodes in immunological reactions of the CNS. The role of regional lymph nodes in immune reactions of the CNS in virus infections, the remote influence of the gut microbiota, multiple sclerosis and stroke are discussed. Evidence is presented for the role of cervical lymph nodes in the induction of tolerance and its influence on neuroimmunological reactions. We look to the future by examining how nanoparticle technology will enhance our understanding of CNS-lymph node connections and by reviewing the implications of lymphatic drainage of the brain for diagnosis and therapy of diseases of the CNS ranging from neuroimmunological disorders to dementias. Finally, we review the challenges and opportunities for progress in CNS-lymph node interactions and their involvement in disease processes.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s11481-013-9470-8

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 23 references

Research works printed but not linked: 98

  1. Andersson PB, Perry VH, Gordon S (1992) 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 · DOI · Paper page
  2. Bailey SL, Schreiner B, McMahon EJ, Miller SD (2007) CNS myeloid DCs presenting endogenous myelin peptides ‘preferentially’ polarize CD4+ T(H)-17 cells in relapsing EAE. Nat Immunol 8(2):172–180. doi:10.1038/ni1430 · DOI · Paper page
  3. Barua NU, Bienemann AS, Hesketh S, Wyatt MJ, Castrique E, Love S, Gill SS (2012) Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical model. Fluids Barriers CNS 9:2. doi:10.1186/2045-8118-9-2 · DOI
  4. Bergsneider M (2001) Evolving concepts of cerebrospinal fluid. Neurosurg Clin N Am 36:631–638 · DOI
  5. Brancato D, Citarrella R, Richiusa P, Amato MC, Vetro C, Galluzzo CG (2013) Neck lymph nodes in chronic autoimmune thyroiditis: the sonographic pattern. Thyroid Off J Am Thyroid Assoc 23(2):173–177. doi:10.1089/thy.2012.0375 · DOI
  6. Bulloch K, Miller MM, Gal-Toth J, Milner TA, Gottfried-Blackmore A, Waters EM, Kaunzner UW, Liu K, Lindquist R, Nussenzweig MC, Steinman RM, McEwen BS (2008) CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain. J Comp Neurol 508:687–710. doi:10.1002/cne.21668 · DOI · Paper page
  7. Burkhart C, Liu GY, Anderton SM, Metzler B, Wraith DC (1999) Peptide-induced T cell regulation of experimental autoimmune encephalomyelitis: a role for IL-10. Int Immunol 11(10):1625–1634 · DOI · Paper page
  8. Carare RO, Bernardes-Silva M, Newman TA, Page AM, Nicoll JAR, Perry VH, Weller RO (2008) Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries. Significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol 34:131–144. doi:10.1111/j.1365-2990.2007.00926 · doi:10.1111/j.1365-2990.2007.00926
  9. Cervantes-Barragan L, Firner S, Bechmann I, Waisman A, Lahl K, Sparwasser T, Thiel V, Ludewig B (2012) Regulatory T cells selectively preserve immune privilege of self-antigens during viral central nervous system infection. J Immunol 188(8):3678–3685. doi:10.4049/jimmunol.1102422 · DOI
  10. Chamorro A, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R (2012) The immunology of acute stroke. Nat Rev Neurol 8(7):401–410. doi:10.1038/nrneurol.2012.98 · DOI · Paper page
  11. Chinnery HR, Ruitenberg MJ, McMenamin PG (2010) Novel characterization of monocyte-derived cell populations in the meninges and choroid plexus and their rates of replenishment in bone marrow chimeric mice. J Neuropathol Exp Neurol 69:896–909. doi:10.1097/NEN.0b013e3181edbc1a · DOI
  12. Clarkson BD, Heninger E, Harris MG, Lee J, Sandor M, Fabry Z (2012) Innate-adaptive crosstalk: how dendritic cells shape immune responses in the CNS. Adv Exp Med Biol 946:309–333. doi:10.1007/978-1-4614-0106-3_18 · DOI
  13. Cserr HF, Knopf PM (1992) Cervical lymphatics, the blood–brain barrier and the immunoreactivity of the brain: a new view. Immunol Today 13(12):507–512 · DOI · Paper page
  14. Cserr HF, Harling-Berg CJ, Knopf PM (1992) Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol 2:269–276 · DOI · Paper page
  15. Davson H, Welch K, Segal MB (1987) Physiology and pathophysiology of the cerebrospinal fluid. Churchill Livingstone, Edinburgh
  16. de Vos AF, van Meurs M, Brok HP, Boven LA, Hintzen RQ, van der Valk P, Ravid R, Rensing S, Boon L, t Hart BA, Laman JD (2002) Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol 169(10):5415–5423 · DOI · Paper page
  17. Deleidi M, Isacson O (2012) Viral and inflammatory triggers of neurodegenerative diseases. Sci Transl Med 4(121):121ps123. doi:10.1126/scitranslmed.3003492 · DOI
  18. Dunne PJ, Moran B, Cummins RC, Mills KH (2009) CD11c+CD8alpha+ dendritic cells promote protective immunity to respiratory infection with Bordetella pertussis. J Immunol 183(1):400–410. doi:10.4049/jimmunol.0900169 · DOI
  19. Engelhardt B (2008) Immune cell entry into the central nervous system: involvement of adhesion molecules and chemokines. J Neurol Sci 274:23–26 · DOI · Paper page
  20. Engelhardt B, Coisne C (2011) Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle. Fluids Barriers CNS 8:4–9 · DOI · Paper page
  21. Fabriek BO, Zwemmer JN, Teunissen CE, Dijkstra CD, Polman CH, Laman JD, Castelijns JA (2005) In vivo detection of myelin proteins in cervical lymph nodes of MS patients using ultrasound-guided fine-needle aspiration cytology. J Neuroimmunol 161:190–194 · DOI
  22. Frenkel D, Puckett L, Petrovic S, Xia W, Chen G, Vega J, Dembinsky-Vaknin A, Shen J, Plante M, Burt DS, Weiner HL (2008) A nasal proteosome adjuvant activates microglia and prevents amyloid deposition. Ann Neurol 63(5):591–601. doi:10.1002/ana.21340 · DOI
  23. Furtado GC, Marcondes MC, Latkowski JA, Tsai J, Wensky A, Lafaille JJ (2008) Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis. J Immunol 181:4648–4655 · DOI
  24. Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18 · DOI · Paper page
  25. Goldmann J, Kwidzinski E, Brandt C, Mahlo J, Richter D, Bechmann I (2006) T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa. J Leukoc Biol 80:797–801. doi:10.1189/jlb.0306176 · DOI · Paper page
  26. Goverman J, Woods A, Larson L, Weiner LP, Hood L, Zaller DM (1993) Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72(4):551–560 · DOI · Paper page
  27. Hamrah P, Dana MR (2007) Corneal antigen-presenting cells. Chem Immunol Allergy 92:58–70. doi:10.1159/000099254 · DOI · Paper page
  28. Hartman KB, Wilson LJ, Rosenblum MG (2008) Detecting and treating cancer with nanotechnology. Mol Diagn Ther 12(1):1–14 · DOI
  29. Hatterer E, Davoust N, Didier-Bazes M, Vuaillat C, Malcus C, Belin MF, Nataf S (2006) How to drain without lymphatics? dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes. Blood 107:806–812 · DOI · Paper page
  30. Hatterer E, Touret M, Belin MF, Honnorat J, Nataf S (2008) Cerebrospinal fluid dendritic cells infiltrate the brain parenchyma and target the cervical lymph nodes under neuroinflammatory conditions. PLoS One 3:e3321. doi:10.1371/journal.pone.0003321 · DOI
  31. Hawkes CA, Hartig W, Kacza J, Schliebs R, Weller RO, Nicoll JA, Carare RO (2011) Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol 121:431–443. doi:10.1007/s00401-011-0801-7 · DOI · Paper page
  32. Hawkes CA, Sullivan PM, Hands S, Weller RO, Nicoll JA, Carare RO (2012) Disruption of arterial perivascular drainage of amyloid-beta from the brains of mice expressing the human APOE epsilon4 allele. PLoS One 7:e41636. doi:10.1371/journal.pone.0041636 · DOI · Paper page
  33. Hochmeister S, Zeitelhofer M, Bauer J, Nicolussi EM, Fischer MT, Heinke B, Selzer E, Lassmann H, Bradl M (2008) After injection into the striatum, in vitro-differentiated microglia- and bone marrow-derived dendritic cells can leave the central nervous system via the blood stream. Am J Pathol 173:1669–1681 · DOI
  34. Ishibashi S, Maric D, Mou Y, Ohtani R, Ruetzler C, Hallenbeck JM (2009) Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 29(3):606–620. doi:10.1038/jcbfm.2008.153 · DOI
  35. Ji Q, Perchellet A, Goverman JM (2010) Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRs. Nat Immunol 11(7):628–634. doi:10.1038/ni.1888 · DOI · Paper page
  36. Ji Q, Castelli L, Goverman JM (2013) MHC class I-restricted myelin epitopes are cross-presented by Tip-DCs that promote determinant spreading to CD8(+) T cells. Nat Immunol 14(3):254–261. doi:10.1038/ni.2513 · DOI
  37. Kaminski M, Bechmann I, Pohland M, Kiwit J, Nitsch R, Glumm J (2012) Migration of monocytes after intracerebral injection at entorhinal cortex lesion site. J Leukoc Biol 92:31–39 · DOI
  38. Karman J, Ling C, Sandor M, Fabry Z (2004) Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol 173:2353–2361 · DOI · Paper page
  39. Keijzer C, Slutter B, van der Zee R, Jiskoot W, van Eden W, Broere F (2011) PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humoral immunity. PLoS One 6(11):e26684. doi:10.1371/journal.pone.0026684 · DOI
  40. Kida S, Pantazis A, Weller RO (1993a) CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 19:480–488 · DOI · Paper page
  41. Kooi EJ, van Horssen J, Witte ME, Amor S, Bo L, Dijkstra CD, van der Valk P, Geurts JJ (2009) Abundant extracellular myelin in the meninges of patients with multiple sclerosis. Neuropathol Appl Neurobiol 35(3):283–295. doi:10.1111/j.1365-2990.2008.00986.x · DOI
  42. Lake J, Weller RO, Phillips MJ, Needham M (1999) Lymphocyte targeting of the brain in adoptive transfer cryolesion-EAE. J Pathol 187(2):259–265 · DOI
  43. Laman JD, Weller RO (2012) Editorial: route by which monocytes leave the brain is revealed. J Leukoc Biol 92:6–9 · DOI
  44. Lieberman SM, Kim JS, Corbo-Rodgers E, Kambayashi T, Maltzman JS, Behrens EM, Turka LA (2012) Site-specific accumulation of recently activated CD4+ Foxp3+ regulatory T cells following adoptive transfer. Eur J Immunol 42(6):1429–1435. doi:10.1002/eji.201142286 · DOI
  45. Ling C, Sandor M, Fabry Z (2003) In situ processing and distribution of intracerebrally injected OVA in the CNS. J Neuroimmunol 141:90–98 · DOI
  46. Locatelli G, Wortge S, Buch T, Ingold B, Frommer F, Sobottka B, Kruger M, Karram K, Buhlmann C, Bechmann I, Heppner FL, Waisman A, Becher B (2012) Primary oligodendrocyte death does not elicit anti-CNS immunity. Nat Neurosci 15:543–550. doi:10.1038/nn.3062 · DOI
  47. Marten NW, Stohlman SA, Zhou J, Bergmann CC (2003) Kinetics of virus-specific CD8+ -T-cell expansion and trafficking following central nervous system infection. J Virol 77(4):2775–2778 · DOI
  48. Mascarell L, Saint-Lu N, Moussu H, Zimmer A, Louise A, Lone Y, Ladant D, Leclerc C, Tourdot S, Van Overtvelt L, Moingeon P (2011) Oral macrophage-like cells play a key role in tolerance induction following sublingual immunotherapy of asthmatic mice. Mucosal Immunol 4(6):638–647. doi:10.1038/mi.2011.28 · DOI
  49. Meredith MM, Liu K, Kamphorst AO, Idoyaga J, Yamane A, Guermonprez P, Rihn S, Yao KH, Silva IT, Oliveira TY, Skokos D, Casellas R, Nussenzweig MC (2012) Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state. J Exp Med 209(9):1583–1593. doi:10.1084/jem.20121003 · DOI
  50. Mohammad MG, Hassanpour M, Tsai VW, Li H, Ruitenberg MJ, Booth DW, Serrats J, Hart PH, Symonds GP, Sawchenko PE, Breit SN, Brown DA (2012) Dendritic cells and multiple sclerosis: disease, tolerance and therapy. Int J Mol Sci 14(1):547–562. doi:10.3390/ijms14010547 · DOI
  51. Moingeon P, Mascarell L (2012) Induction of tolerance via the sublingual route: mechanisms and applications. Clin Dev Immunol 2012:623474. doi:10.1155/2012/623474 · DOI
  52. Monteiro M, Almeida CF, Caridade M, Ribot JC, Duarte J, Agua-Doce A, Wollenberg I, Silva-Santos B, Graca L (2010) Identification of regulatory Foxp3+ invariant NKT cells induced by TGF-beta. J Immunol 185(4):2157–2163. doi:10.4049/jimmunol.1000359 · DOI
  53. Muldoon LL, Varallyay P, Kraemer DF, Kiwic G, Pinkston K, Walker-Rosenfeld SL, Neuwelt EA (2004) Trafficking of superparamagnetic iron oxide particles (Combidex) from brain to lymph nodes in the rat. Neuropathol Appl Neurobiol 30(1):70–79 · DOI
  54. Mutlu L, Brandt C, Kwidzinski E, Sawitzki B, Gimsa U, Mahlo J, Aktas O, Nitsch R, van Zwam M, Laman JD, Bechmann I (2007) Tolerogenic effect of fiber tract injury: reduced EAE severity following entorhinal cortex lesion. Exp Brain Res 178:542–553 · DOI
  55. Navarrete-Talloni MJ, Kalkuhl A, Deschl U, Ulrich R, Kummerfeld M, Rohn K, Baumgartner W, Beineke A (2010) Transient peripheral immune response and central nervous system leaky compartmentalization in a viral model for multiple sclerosis. Brain Pathol 20(5):890–901. doi:10.1111/j.1750-3639.2010.00383.x · DOI
  56. Nicholas DS, Weller RO (1988) The fine anatomy of the human spinal meninges. A light and scanning electron microscopy study. J Neurosurg 69:276–282 · DOI · Paper page
  57. Ochoa-Reparaz J, Mielcarz DW, Ditrio LE, Burroughs AR, Foureau DM, Haque-Begum S, Kasper LH (2009) Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol 183(10):6041–6050. doi:10.4049/jimmunol.0900747 · DOI · Paper page
  58. Ochoa-Reparaz J, Mielcarz DW, Wang Y, Begum-Haque S, Dasgupta S, Kasper DL, Kasper LH (2010b) A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol 3(5):487–495. doi:10.1038/mi.2010.29 · DOI · Paper page
  59. Odoardi F, Sie C, Streyl K, Ulaganathan VK, Schlager C, Lodygin D, Heckelsmiller K, Nietfeld W, Ellwart J, Klinkert WE, Lottaz C, Nosov M, Brinkmann V, Spang R, Lehrach H, Vingron M, Wekerle H, Flugel-Koch C, Flugel A (2012) T cells become licensed in the lung to enter the central nervous system. Nature 488(7413):675–679. doi:10.1038/nature11337 · DOI · Paper page
  60. Oude Engberink RD, Blezer EL, Dijkstra CD, van der Pol SM, van der Toorn A, de Vries HE (2010) Dynamics and fate of USPIO in the central nervous system in experimental autoimmune encephalomyelitis. NMR Biomed 23(9):1087–1096. doi:10.1002/nbm.1536 · DOI
  61. Ousman SS, Kubes P (2012) Immune surveillance in the central nervous system. Nat Neurosci 15(8):1096–1101. doi:10.1038/nn.3161 · DOI · Paper page
  62. Pachter JS, de Vries HE, Fabry Z (2003) The blood–brain barrier and its role in immune privilege in the central nervous system. J Neuropathol Exp Neurol 62:593–604 · DOI · Paper page
  63. Phillips MJ, Needham M, Weller RO (1997) Role of cervical lymph nodes in autoimmune encephalomyelitis in the Lewis rat. J Pathol 182:457–464 · DOI
  64. Planas AM, Gomez-Choco M, Urra X, Gorina R, Caballero M, Chamorro A (2012) Brain-derived antigens in lymphoid tissue of patients with acute stroke. J Immunol 188(5):2156–2163. doi:10.4049/jimmunol.1102289 · DOI · Paper page
  65. Ploix CC, Noor S, Crane J, Masek K, Carter W, Lo DD, Wilson EH, Carson MJ (2011) CNS-derived CCL21 is both sufficient to drive homeostatic CD4+ T cell proliferation and necessary for efficient CD4+ T cell migration into the CNS parenchyma following Toxoplasma gondii infection. Brain Behav Immun 25(5):883–896. doi:10.1016/j.bbi.2010.09.014 · DOI
  66. Preston SD, Steart PV, Wilkinson A, Nicoll JAR, Weller RO (2003) Capillary and arterial amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol 29:106–117 · DOI · Paper page
  67. Ransohoff RM (2010) Turning over the chance card on MS susceptibility. Nat Immunol 11(7):570–572. doi:10.1038/ni0710-570 · DOI
  68. Ransohoff RM (2012) Animal models of multiple sclerosis: the good, the bad and the bottom line. Nat Neurosci 15(8):1074–1077. doi:10.1038/nn.3168 · DOI · Paper page
  69. Ransohoff RM, Engelhardt B (2012) The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 12(9):623–635. doi:10.1038/nri3265 · DOI · Paper page
  70. Rynda A, Maddaloni M, Mierzejewska D, Ochoa-Reparaz J, Maslanka T, Crist K, Riccardi C, Barszczewska B, Fujihashi K, McGhee JR, Pascual DW (2008) Low-dose tolerance is mediated by the microfold cell ligand, reovirus protein sigma1. J Immunol 180(8):5187–5200 · DOI
  71. Samsom JN, Hauet-Broere F, Unger WW, Vanb LA, Kraal G (2004) Early events in antigen-specific regulatory T cell induction via nasal and oral mucosa. Ann N Y Acad Sci 1029:385–389. doi:10.1196/annals.1309.045 · doi:10.1196/annals.1309.045
  72. Samsom JN, van Berkel LA, van Helvoort JM, Unger WW, Jansen W, Thepen T, Mebius RE, Verbeek SS, Kraal G (2005) Fc gamma RIIB regulates nasal and oral tolerance: a role for dendritic cells. J Immunol 174(9):5279–5287 · doi:10.4049/jimmunol.174.9.5279
  73. Samsom JN, van der Marel AP, van Berkel LA, van Helvoort JM, Simons-Oosterhuis Y, Jansen W, Greuter M, Nelissen RL, Meeuwisse CM, Nieuwenhuis EE, Mebius RE, Kraal G (2007) Secretory leukoprotease inhibitor in mucosal lymph node dendritic cells regulates the threshold for mucosal tolerance. J Immunol 179(10):6588–6595 · doi:10.4049/jimmunol.179.10.6588
  74. Schwalbe G (1869) Der Arachnoidalraum, ein Lymphraum und sein Zusammenhang mit dem Perichoroidalraum. Zentralb Med Wiss 7:465–467
  75. Serot JM, Foliguet B, Bene MC, Faure GC (1997) Ultrastructural and immunohistological evidence for dendritic-like cells within human choroid plexus epithelium. Neuroreport 8:1995–1998 · DOI
  76. Sun D, Tani M, Newman TA, Krivacic K, Phillips M, Chernosky A, Gill P, Wei T, Griswold KJ, Ransohoff RM, Weller RO (2000) Role of chemokines, neuronal projections, and the blood–brain barrier in the enhancement of cerebral EAE following focal brain damage. J Neuropathol Exp Neurol 59:1031–1043 · DOI
  77. Szentistvanyi I, Patlak CS, Ellis RA, Cserr HF (1984) Drainage of interstitial fluid from different regions of rat brain. Am J Physiol 246:F835–F844
  78. Trandem K, Anghelina D, Zhao J, Perlman S (2010) Regulatory T cells inhibit T cell proliferation and decrease demyelination in mice chronically infected with a coronavirus. J Immunol 184(8):4391–4400. doi:10.4049/jimmunol.0903918 · DOI
  79. Tripathi BJ, Tripathi RC (1974) Vacuolar transcellular channels as a drainage pathway for cerebrospinal fluid. J Physiol 239:195–206 · DOI
  80. Tschen SI, Stohlman SA, Ramakrishna C, Hinton DR, Atkinson RD, Bergmann CC (2006) CNS viral infection diverts homing of antibody-secreting cells from lymphoid organs to the CNS. Eur J Immunol 36(3):603–612. doi:10.1002/eji.200535123 · DOI
  81. van Helvoort JM, Samsom JN, Chantry D, Jansen W, Schadee-Eestermans I, Thepen T, Mebius RE, Kraal G (2004) Preferential expression of IgG2b in nose draining cervical lymph nodes and its putative role in mucosal tolerance induction. Allergy 59(11):1211–1218. doi:10.1111/j.1398-9995.2004.00510.x · doi:10.1111/j.1398-9995.2004.00510.x
  82. van Zwam M, Huizinga R, Heijmans N, van Meurs M, Wierenga-Wolf AF, Melief M-J, Hintzen RQ, ’t Hart BA, Amor S, Boven LA, Laman JD (2009a) Surgical excision of CNS-draining lymph nodes reduces relapse severity in chronic-relapsing EAE. J Pathol 217:543–551 · DOI
  83. van Zwam M, Huizinga R, Melief MJ, Wierenga-Wolf AF, van Meurs M, Voerman JS, Biber KP, Boddeke HW, Höpken UE, Meisel C, Meisel A, Bechmann I, Hintzen RQ, ’t Hart BA, Amor S, Laman JD, Boven LA (2009b) Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE. J Mol Med 87:273–286 · DOI
  84. von Budingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J, Cree BA, Gourraud PA, Schwartzburg A, Huerta G, Telman D, Sundar PD, Casey T, Cox DR, Hauser SL (2012) B cell exchange across the blood–brain barrier in multiple sclerosis. J Clin Investig 122(12):4533–4543. doi:10.1172/JCI63842 · DOI · Paper page
  85. Wang SH, Fan Y, Makidon PE, Cao Z, Baker JR (2012) Induction of immune tolerance in mice with a novel mucosal nanoemulsion adjuvant and self-antigen. Nanomedicine (London) 7(6):867–876. doi:10.2217/nnm.11.187 · doi:10.2217/nnm.11.187
  86. Weller RO (1999) Reaction of intrathecal and epidural spaces to infection and inflammation. In: Yaksh TL (ed) Spinal drug delivery. Elsevier, Amsterdam, pp 297–315
  87. Weller RO (2005) Microscopic morphology and histology of the human meninges. Morphologie 89:22–34 · DOI · Paper page
  88. Weller RO, Subash M, Preston SD, Mazanti I, Carare RO (2008) Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol 18:253–266 · DOI · Paper page
  89. Weller RO, Galea I, Carare RO, Minagar A (2010) Pathophysiology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis. Pathophysiol Off J Int Soc Pathophysiol/ISP 17:295–306
  90. Willart MA, Jan de Heer H, Hammad H, Soullie T, Deswarte K, Clausen BE, Boon L, Hoogsteden HC, Lambrecht BN (2009) The lung vascular filter as a site of immune induction for T cell responses to large embolic antigen. J Exp Med 206(12):2823–2835. doi:10.1084/jem.20082401 · DOI
  91. Wolvers DA, Coenen-de Roo CJ, Mebius RE, van der Cammen MJ, Tirion F, Miltenburg AM, Kraal G (1999) Intranasally induced immunological tolerance is determined by characteristics of the draining lymph nodes: studies with OVA and human cartilage gp-39. J Immunol 162:1994–1998 · DOI · Paper page
  92. Yamazaki S, Maruyama A, Okada K, Matsumoto M, Morita A, Seya T (2012) Dendritic cells from oral cavity induce Foxp3(+) regulatory T cells upon antigen stimulation. PLoS One 7(12):e51665. doi:10.1371/journal.pone.0051665 · DOI
  93. Yogev N, Frommer F, Lukas D, Kautz-Neu K, Karram K, Ielo D, von Stebut E, Probst HC, van den Broek M, Riethmacher D, Birnberg T, Blank T, Reizis B, Korn T, Wiendl H, Jung S, Prinz M, Kurschus FC, Waisman A (2012) Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells. Immunity 37(2):264–275. doi:10.1016/j.immuni.2012.05.025 · DOI · Paper page
  94. Zhang ET, Inman CB, Weller RO (1990) Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum. J Anat 170:111–123
  95. Zhang ET, Richards HK, Kida S, Weller RO (1992) Directional and compartmentalised drainage of interstitial fluid and cerebrospinal fluid from the rat brain. Acta Neuropathol 83:233–239 · DOI · Paper page
  96. Zhang H, Podojil JR, Luo X, Miller SD (2008) Intrinsic and induced regulation of the age-associated onset of spontaneous experimental autoimmune encephalomyelitis. J Immunol 181(7):4638–4647 · DOI
  97. Zhong Y, Wang X, Ji Q, Mao X, Tang H, Yi G, Meng K, Yang X, Zeng Q (2012) CD4+LAP + and CD4 +CD25 +Foxp3 + regulatory T cells induced by nasal oxidized low-density lipoprotein suppress effector T cells response and attenuate atherosclerosis in ApoE-/- mice. J Clin Immunol 32(5):1104–1117. doi:10.1007/s10875-012-9699-7 · DOI
  98. Zwillinger H (1912) Die Lymphbahnen des oberen Nasalschnittes und deren Beziehungen zu den perimeningealen Lymphraumen. Arch Laryngol und Rhinol 26:66–78

Cited by

See all 166

Metadata

Authors
Laman, J. D., & Weller, R. O.
Venue
Journal of Neuroimmune Pharmacology
Publisher
Springer Science and Business Media LLC
Published
2013-05-22
Volume
8
Issue
4
Pages
840-856
ISSN
  • 1557-1890 (ISSN-L)
  • 1557-1904
DOI
10.1007/s11481-013-9470-8
OpenAlex
W2034990013
Cited by
166
References
23
FWCI
6.70
Type
journal article
Language
en
Open access
bronze
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes. https://app.cochat.ai/papers/10.1007/s11481-013-9470-8
The paper
Laman, J. D., & Weller, R. O. (2013). Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes. Journal of Neuroimmune Pharmacology. https://doi.org/10.1007/s11481-013-9470-8

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.