What is immune privilege (not)?

Galea, Ian; Bechmann, Ingo; Perry, V. Hugh

doi:10.1016/j.it.2006.11.004

Cited by 768Neuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function StudiesT-cell and B-cell Immunology

What is immune privilege (not)?

Galea, Ian, Bechmann, Ingo, Perry, V. Hugh·2007·Trends in Immunology

DOI 10.1016/j.it.2006.11.004

Open this paper in CoChat — free account

Abstract

The 'immune privilege' of the central nervous system (CNS) is indispensable for damage limitation during inflammation in a sensitive organ with poor regenerative capacity. It is a longstanding notion which, over time, has acquired several misconceptions and a lack of precision in its definition. In this article, we address these issues and re-define CNS immune privilege in the light of recent data. We show how it is far from absolute, and how it varies with age and brain region. Immune privilege in the CNS is often mis-attributed wholly to the blood-brain barrier. We discuss the pivotal role of the specialization of the afferent arm of adaptive immunity in the brain, which results in a lack of cell-mediated antigen drainage to the cervical lymph nodes although soluble drainage to these nodes is well described. It is now increasingly recognized how immune privilege is maintained actively as a result of the immunoregulatory characteristics of the CNS-resident cells and their microenvironment.

Integrity signals

Registry

Crossref · 10.1016/j.it.2006.11.004

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The CNS parenchyma does not have a conventional lymphatic drainage system.
“Although the CNS parenchyma does not have a conventional lymphatic drainage system (3), lymphatics have been discovered in the dura mater and just outside holes in the skull bone (4-9).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [3]

CYCLOOXYGENASES 1 AND 2
Vane, J. R., Bakhle, Y. S., & Botting, R. M. (1998) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.38.1.97 · Cited by 2,737 · see citing works
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · see citing works
Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis.
Serafini, B., Rosicarelli, B., Magliozzi, R., Stigliano, E., & Aloisi, F. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00049.x · Cited by 1,208 · see citing works
Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2
Takahashi, K., Rochford, C. D. P., & Neumann, H. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041611 · Cited by 1,124 · see citing works
Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye.
Medawar, P. B. (1948) · PubMed · Cited by 1,084 · see citing works
Down-Regulation of the Macrophage Lineage Through Interaction with OX2 (CD200)
Hoek, R. M., Ruuls, S. R., Murphy, C. A., Wright, G. J., Goddard, R., Zurawski, S. M., Blom, B., Homola, M. E., Streit, W. J., Brown, M. H., et al. (2000) · Science · doi:10.1126/science.290.5497.1768 · Cited by 1,022 · see citing works
Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis
McMahon, E. J., Bailey, S. L., Castenada, C. V., Waldner, H., & Miller, S. D. (2005) · Nature Medicine · doi:10.1038/nm1202 · Cited by 694 · see citing works
Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared
Ford, A. L., Goodsall, A. L., Hickey, W. F., & Sedgwick, J. D. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.9.4309 · Cited by 631 · see citing works
The Shorter Oxford English Dictionary
Rice, W., Little, W. C., & Onions, C. T. (1937) · The English Journal · doi:10.2307/804556 · Cited by 594 · see citing works
CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance
Kida, S., Pantazis, A., & Weller, R. O. (1993) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1993.tb00476.x · Cited by 520 · see citing works
CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis.
Gerritse, K., Laman, J. D., Noelle, R. J., Aruffo, A. A., Ledbetter, J. A., Boersma, W. J., & Claassen, E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.6.2499 · Cited by 484 · see citing works
See no evil, hear no evil, do no evil: the lessons of immune privilege
Niederkorn, J. Y. (2006) · Nature Immunology · doi:10.1038/ni1328 · Cited by 449 · see citing works
Brain microglia constitutively express β-2 integrins
Akiyama, H., & McGeer, P. L. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90055-r · Cited by 430 · see citing works
Treatment of Autoimmune Neuroinflammation with a Synthetic Tryptophan Metabolite
Platten, M., Ho, P. P.-K., Youssef, S., da Fontoura, P. P., Garren, H., Hur, E. M., Gupta, R. K., Lee, L. Y., Kidd, B. A., Robinson, W. H., et al. (2005) · Science · doi:10.1126/science.1117634 · Cited by 427 · see citing works
Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord
Schnell, L., Fearn, S., Klassen, H. J., Schwab, M. E., & Perry, V. H. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00792.x · Cited by 410 · see citing works
Self-citation
Lymphoid/Neuronal Cell Surface OX2 Glycoprotein Recognizes a Novel Receptor on Macrophages Implicated in the Control of Their Function
Wright, G. J., Puklavec, M. J., Willis, A. C., Hoek, R. M., Sedgwick, J. D., Brown, M. H., & Barclay, A. N. (2000) · Immunity · doi:10.1016/s1074-7613(00)00023-6 · Cited by 388 · see citing works
Altered antigen expression of microglia in the aged rodent CNS
Perry, V. H., Matyszak, M. K., & Fearn, S. (1993) · Glia · doi:10.1002/glia.440070111 · Cited by 364 · see citing works
Self-citation
Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis
Corcione, A., Casazza, S., Ferretti, E., Giunti, D., Zappia, E., Pistorio, A., Gambini, C., Mancardi, G., Uccelli, A., & Pistoia, V. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402455101 · Cited by 349 · see citing works
Complement components of the innate immune system in health and disease in the CNS
Gasque, P., Dean, Y. D., McGreal, E. P., VanBeek, J., & Morgan, B. P. (2000) · Immunopharmacology · doi:10.1016/s0162-3109(00)80302-1 · Cited by 343 · see citing works
The acute inflammatory response to lipopolysaccharide in cns parenchyma differs from that in other body tissues
Andersson, P.-B., Perry, V. H., & Gordon†, S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90347-5 · Cited by 324 · see citing works
Self-citation
Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis
Magliozzi, R., Cabezas, S. C., Serafini, B., & Aloisi, F. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2003.10.056 · Cited by 317 · see citing works
Indolamine 2,3‐dioxygenase is expressed in the CNS and down‐regulates autoimmune inflammation
Kwidzinski, E., Bunse, J., Aktas, O., Richter, D., Mutlu, L., Zipp, F., Nitsch, R., & Bechmann, I. (2005) · The FASEB Journal · doi:10.1096/fj.04-3228fje · Cited by 304 · see citing works
Self-citation
Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE
Liu, Y., Teige, I., Birnir, B., & Issazadeh‐Navikas, S. (2006) · Nature Medicine · doi:10.1038/nm1402 · Cited by 302 · see citing works
Major Histocompatibility Complex (MHC) Class I Gene Expression in Single Neurons of the Central Nervous System: Differential Regulation by Interferon (IFN)-γ and Tumor Necrosis Factor (TNF)-α
Neumann, H., Schmidt, H., Cavalié, A., Jenne, D. E., & Wekerle, H. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.2.305 · Cited by 288 · see citing works
The fate of allogeneic and xenogeneic neuronal tissue transplanted into the third ventricle of rodents
Mason, D., Charlton, H. M., Jones, A. J., et al. (1986) · Neuroscience · doi:10.1016/0306-4522(86)90292-7 · Cited by 286 · see citing works
Neurotrophins inhibit major histocompatibility class II inducibility of microglia: Involvement of the p75 neurotrophin receptor
Neumann, H., Misgeld, T., Matsumuro, K., & Wekerle, H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.10.5779 · Cited by 282 · see citing works
Transfer of Central Nervous System Autoantigens and Presentation in Secondary Lymphoid Organs
de Vos, A. F., van Meurs, M., Brok, H., Boven, L. A., Hintzen, R. Q., van der Valk, P., Ravid, R., Rensing, S., Boon, L., Hart, B. A. ‘., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5415 · Cited by 278 · see citing works
A revised view of the central nervous system microenvironment and major histocompatibility complex class II antigen presentation
Perry, V. H. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00145-3 · Cited by 276 · see citing works
Self-citation
Signal-Regulatory Protein Is Selectively Expressed by Myeloid and Neuronal Cells
Adams, S., van der Laan, L. J. W., Vernon-Wilson, E. F., de Lavalette, C. R., Döpp, E. A., Dijkstra, C. D., Simmons, D. L., & van den Berg, T. K. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.4.1853 · Cited by 260 · see citing works
IL-12 production by central nervous system microglia is inhibited by astrocytes
Aloisi, F., Penna, G., Cerase, J., Iglesias, B. M., & Adorini, L. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.4.1604 · Cited by 252 · see citing works
Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in rats
Anthony, D. C. (1997) · Brain · doi:10.1093/brain/120.3.435 · Cited by 252 · see citing works
CONDITIONS DETERMINING THE TRANSPLANTABILITY OF TISSUES IN THE BRAIN
Murphy, J. B., & Sturm, E. (1923) · Journal of Experimental Medicine · doi:10.1084/jem.38.2.183 · Cited by 246 · see citing works
Initiation of Immune Responses in Brain Is Promoted by Local Dendritic Cells
Kármán, J., Ling, C., Sándor, M., & Fábry, Z. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.4.2353 · Cited by 240 · see citing works
Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system.
Vass, K., & Lassmann, H. (1990) · Europe PMC (PubMed Central) · Cited by 238 · see citing works
The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system
Matyszak, M. K., & Perry, V. H. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00160-1 · Cited by 234 · see citing works
Self-citation
In vivo expression of alternatively spliced forms of integrin-associated protein (cd47)
Reinhold, M. I., Lindberg, F. P., Plas, D. R., Reynolds, S., Peters, M. G., & Brown, E. J. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.11.3419 · Cited by 233 · see citing works
Modulation of CD4 antigen on macrophages and microglia in rat brain.
Perry, V. H., & Gordon, S. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.166.4.1138 · Cited by 229 · see citing works
Self-citation
Role of the peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) and its natural ligand 15‐deoxy‐Δ<sup>12,14</sup>‐prostaglandin J<sub>2</sub>in the regulation of microglial functions
Bernardo, A., Levi, G., & Minghetti, L. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00110.x · Cited by 222 · see citing works
FasL (CD95L, Apo1L) is expressed in the normal rat and human brain: Evidence for the existence of an immunological brain barrier
Bechmann, I., Mor, G., Nilsen, J., Eliza, M., Nitsch, R., & Naftolin, F. N. (1999) · Glia · doi:10.1002/(sici)1098-1136(199907)27:1 · Cited by 221 · see citing works
Self-citation
Enhanced expression of transforming growth factor β1 in the rat brain after a localized cerebral injury
Logan, A., Frautschy, S. A., González, A.-M., Sporn, M. B., & Baird, A. (1992) · Brain Research · doi:10.1016/0006-8993(92)91000-5 · Cited by 220 · see citing works
Distribution of extracellular tracers in perivascular spaces of the rat brain
Ichimura, T., Fraser, P. A., & Cserr, H. F. (1991) · Brain Research · doi:10.1016/0006-8993(91)91275-6 · Cited by 215 · see citing works
Signal Regulatory Proteins in the Immune System
van Beek, E. M., Cochrane, F., Barclay, A. N., & van den Berg, T. K. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.12.7781 · Cited by 204 · see citing works
Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells
Ulvestad, E., Williams, K. C., Bjerkvig, R., Tiekotter, K. L., Antel, J. P., & Matre, R. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.56.6.732 · Cited by 203 · see citing works
The Costimulatory Molecule B7 is Expressed on Human Microglia in Culture and in Multiple Sclerosis Acute Lesions
Simone, R. D., Giampaolo, A., Giometto, B., Gallo, P., Levi, G., Peschle, C., & Aloisi, F. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199503000-00004 · Cited by 201 · see citing works
T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa
Goldmann, J., Kwidzinski, E., Brandt, C., Mahlo, J., Richter, D., & Bechmann, I. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306176 · Cited by 188 · see citing works
Self-citation
Intranasally Induced Immunological Tolerance Is Determined by Characteristics of the Draining Lymph Nodes: Studies with OVA and Human Cartilage gp-39
Wolvers, D. A. W., Roo, C. J. J. C., Mebius, R. E., van der Cammen, M. J. F., Tirion, F. H., Miltenburg, A. M. M., & Kraal, G. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.4.1994 · Cited by 177 · see citing works
Studies on the problem of corneal homografts
Billingham, R. E., & Boswell, T. (1953) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1953.0049 · Cited by 175 · see citing works
Neuronal expression of CD22: Novel mechanism for inhibiting microglial proinflammatory cytokine production
Mott, R. T., Ait‐Ghezala, G., Town, T., Mori, T., Vendrame, M., Zeng, J., Ehrhart, J. C., MULLAN, M. J., & Tan, J. (2004) · Glia · doi:10.1002/glia.20009 · Cited by 171 · see citing works
Albumin outflow into deep cervical lymph from different regions of rabbit brain
Yamada, S., Depasquale, M. J., Patlak, C. S., & Cserr, H. F. (1991) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1991.261.4.h1197 · Cited by 165 · see citing works
How to drain without lymphatics? Dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes
Hatterer, E., Davoust, N., Didier‐Bazès, M., Vuaillat, C., Malcus, C., Belin, M., & Nataf, S. (2005) · Blood · doi:10.1182/blood-2005-01-0154 · Cited by 163 · see citing works
Microglial Expression of the B7 Family Member B7 Homolog 1 Confers Strong Immune Inhibition: Implications for Immune Responses and Autoimmunity in the CNS
Magnus, T., Schreiner, B., Korn, T., Jack, C. S., Guo, H., Antel, J. P., Ifergan, I., Chen, L., Bischof, F., Bar‐Or, A., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4794-04.2005 · Cited by 160 · see citing works
Immunological Instability of Persistent Adenovirus Vectors in the Brain: Peripheral Exposure to Vector Leads to Renewed Inflammation, Reduced Gene Expression, and Demyelination
Byrnes, A. P., MacLaren, R. E., & Charlton, H. M. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-09-03045.1996 · Cited by 155 · see citing works
T-Cell Apoptosis in Inflammatory Brain Lesions
Bauer, J., Bradl, M., Hickey, W. F., Forss‐Petter, S., Breitschopf, H., Linington, C., Wekerle, H., & Lassmann, H. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65615-5 · Cited by 146 · see citing works
Blood monocytes and spleen macrophages differentiate into microglia‐like cells on monolayers of astrocytes: Morphology
Sievers, J., Parwaresch, R. M., & Wottge, H. ‐. (1994) · Glia · doi:10.1002/glia.440120402 · Cited by 138 · see citing works
Correlation analysis between frequencies of circulating antigen-specific IgG-bearing memory B cells and serum titers of antigen-specific IgG
Leyendeckers, H., Odendahl, M., Löhndorf, A., Irsch, J., Spangfort, M. D., Miltenyi, S., Hunzelmann, N., Assenmacher, M., Radbruch, A., & Schmitz, J. (1999) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199904)29:04 · Cited by 135 · see citing works
Role of the cervical lymphatics in the Th2-type hierarchy of CNS immune regulation1This work was supported by National Institute of Health Grant (RO1 NS33070-03) and The Brain Tumor Society.1
Harling‐Berg, C. J., Park, J. T., & Knopf, P. M. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00130-7 · Cited by 134 · see citing works
Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions
Levi, G., Minghetti, L., & Aloisi, F. (1998) · Biochimie · doi:10.1016/s0300-9084(00)88886-0 · Cited by 133 · see citing works
Astrocytes as eicosanoid‐producing cells
Murphy, S. P., Pearce, B., Jeremy, J., & Dandona, P. (1988) · Glia · doi:10.1002/glia.440010402 · Cited by 121 · see citing works
See No Evil
Baer, R. M. (2003) · Cited by 121 · see citing works
The immunogenicity of intracerebral virus infection depends on anatomical site
Stevenson, P. G., Hawke, S., Sloan, D. J., & Bangham, C. R. (1997) · Journal of Virology · doi:10.1128/jvi.71.1.145-151.1997 · Cited by 114 · see citing works
Intracerebral injections and the growth of viruses in the mouse brain.
MIMS, C. A. (1960) · PubMed · Cited by 104 · see citing works
Demyelination in the central nervous system following a delayed-type hypersensitivity response to bacillus Calmette-Guérin
Matyszak, M. K., & Perry, V. H. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00448-e · Cited by 102 · see citing works
Self-citation
Leukocyte infiltration and glial reactions in xenografts of mouse brain tissue undergoing rejection in the adult rat brain. A light and electron microscopical immunocytochemical study
Finsen, B. R., Sørensen, T., Castellano, B., Pedersen, E. B., & Zimmer, J. (1991) · Journal of Neuroimmunology · doi:10.1016/0165-5728(91)90008-u · Cited by 102 · see citing works
Disproportionate Recruitment of CD8+ T Cells into the Central Nervous System by Professional Antigen-Presenting Cells
Carson, M. J., Reilly, C. R., Sutcliffe, J. G., & Lo, D. D. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65294-7 · Cited by 98 · see citing works
Recruitment of dendritic cells to the cerebrospinal fluid in bacterial neuroinfections
Pashenkov, M. V., Teleshova, N., Kouwenhoven, M. C. M., Смирнова, Т. А., Jin, Y.-P., Kostulas, V., Huang, Y.-M., Pinegin, B. V., Boiko, A. N., & Link, H. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00451-9 · Cited by 95 · see citing works
The blood-brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia
Perry, V. H., Crocker, P. R., & Gordon, S. (1992) · Journal of Cell Science · doi:10.1242/jcs.101.1.201 · Cited by 95 · see citing works
Self-citation
TGFβ1 regulates the inflammatory response during chronic neurodegeneration
Boche, D., Cunningham, C. M., Docagne, F., Scott, H., & Perry, V. H. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.01.004 · Cited by 89 · see citing works
Self-citation
Multiple sclerosis Immunomodulatory effects of human astrocytes on T cells
Meinl, E., Aloisi, F., Ertl-Wagner, B. B., et al. (1994) · Brain · doi:10.1093/brain/117.6.1323 · Cited by 87 · see citing works
Blood monocytes and spleen macrophages differentiate into microglia‐like cells on monolayers of astrocytes: Membrane currents
Schmidtmayer, J., Jacobsen, C. B., Miksch, G., & Sievers, J. (1994) · Glia · doi:10.1002/glia.440120403 · Cited by 86 · see citing works
HLA class II molecules (HLA-DR, -DP, -DQ) on cells in the human CNS studied in situ and in vitro.
Ulvestad, E., Williams, K. C., Bø, L., Trapp, B. D., Antel, J. P., & Mörk, S. (1994) · PubMed Central · Cited by 81 · see citing works
Transforming growth factor β1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix
Cunningham, C. M., Boche, D., & Perry, V. H. (2002) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2002.00383.x · Cited by 80 · see citing works
Self-citation
Systemic Immune Deviation in the Brain That Does Not Depend on the Integrity of the Blood-Brain Barrier
Wenkel, H., Streilein, J. W., & Young, M. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.5125 · Cited by 79 · see citing works
Astrocyte‐induced regulatory T cells mitigate CNS autoimmunity
Trajković, V., Vuckovic, O., Stošić‐Grujičić, S., Miljković, D. M., Popadic, D. M., Marković, M., Bumbasirevic, V. Z., Backović, A., Cvetković, I., Harhaji-Trajkovic, L. M., et al. (2004) · Glia · doi:10.1002/glia.20046 · Cited by 78 · see citing works
Myelin basic protein infused into cerebrospinal fluid suppresses experimental autoimmune encephalomyelitis
Harling‐Berg, C. J., Knopf, P. M., & Cserr, H. F. (1991) · Journal of Neuroimmunology · doi:10.1016/0165-5728(91)90160-9 · Cited by 74 · see citing works
Macrophage Markers in Diagnostic Neuropathology
Hulette, C. M., Downey, B. T., & Burger, P. C. (1992) · The American Journal of Surgical Pathology · doi:10.1097/00000478-199205000-00008 · Cited by 72 · see citing works
The Unique Characteristics of Inflammatory Responses in Mouse Brain are Acquired During Postnatal Development
Lawson, L. J., & Perry, V. H. (1995) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1995.tb01154.x · Cited by 66 · see citing works
Self-citation
Differential induction of interleukin-1β and tumour necrosis factor-α may account for specific patterns of leukocyte recruitment in the brain
Blond, D., Campbell, S. J., Butchart, A. G., Perry, V. H., & Anthony, D. C. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03473-x · Cited by 64 · see citing works
Self-citation
Glial Cell Developmentbasic principles and clinical relevance
Jessen, K. R., & Richardson, W. D. (1997) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9781872748542.001.0001 · Cited by 62 · see citing works
Lymphatic efflux of intracerebrally injected cells
Oehmichen, M., Gr�ninger, H., Wieth�lter, H., & Genčić, M. (1979) · Acta Neuropathologica · doi:10.1007/bf00691806 · Cited by 52 · see citing works
Bacillus Calmette–Guérin sequestered in the brain parenchyma escapes immune recognition
Matyszak, M. K., & Perry, V. H. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00190-2 · Cited by 49 · see citing works
Self-citation
Distribution and Immunophenotype of DC-SIGN-Expressing Cells in SIV-Infected and Uninfected Macaques
Schwartz, A. J., Alvarez, X. A., & Lackner, A. A. (2002) · AIDS Research and Human Retroviruses · doi:10.1089/08892220260235380 · Cited by 46 · see citing works
APCs in the Anterior Uveal Tract Do Not Migrate to Draining Lymph Nodes
Dullforce, P. A., Garman, K. L., Seitz, G. W., Fleischmann, R. J., Crespo, S. M., Planck, S. R., Parker, D. C., & Rosenbaum, J. T. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.11.6701 · Cited by 44 · see citing works
A comparison of leucocyte responses to heat‐killed bacillus Calmette‐Guérin in different CNS compartments
Matyszak, M. K., & Perry, V. H. (1996) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1996.tb00845.x · Cited by 40 · see citing works
Self-citation
Anatomical and Cellular Requirements for the Activation and Migration of Virus-Specific CD8+T Cells to the Brain during Theiler's Virus Infection
Mendez-Fernandez, Y., Hansen, M. J., Rodriguez, M., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.5.3063-3070.2005 · Cited by 28 · see citing works
Dendritic cell recruitment following xenografting of pig fetal mesencephalic cells into the rat brain
Michel, D. C., Nerrière‐Daguin, V., Josien, R., Brachet, P., Naveilhan, P., & Neveu, I. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.05.021 · Cited by 20 · see citing works
Microglia in the developing and mature central nervous system
Perry, V. H. (1997) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9781872748542.003.0007 · Cited by 8 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395 · see citing works
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · see citing works
The Pathobiology of Vascular Dementia
Iadecola, C. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.008 · Cited by 1,857 · see citing works
“The perivascular space, which drains into the subarachnoid space and then into cervical lymphnodes (Laman and Weller, 2013), is the ‘‘afferent arm’’ through which brain antigens reach the systemic immune system (Galea et al., 2007).”
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · see citing works
Self-citation
Astrocytes are active players in cerebral innate immunity
Farina, C., Aloisi, F., & Meinl, E. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.01.005 · Cited by 1,304 · see citing works
Astrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202 · see citing works
The movers and shapers in immune privilege of the CNS
Engelhardt, B., Vajkoczy, P., & Weller, R. O. (2017) · Nature Immunology · doi:10.1038/ni.3666 · Cited by 893 · see citing works
The myeloid cells of the central nervous system parenchyma
Ransohoff, R. M., & Cardona, A. E. (2010) · Nature · doi:10.1038/nature09615 · Cited by 804 · see citing works
Neuronal ‘On’ and ‘Off’ signals control microglia
Biber, K., Neumann, H., Inoue, K., & Boddeke, H. W. G. M. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.08.007 · Cited by 787 · see citing works
Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology
Carare, R. O., Bernardes‐Silva, M., Newman, T. A., Page, A. M., Nicoll, J. A. R., Perry, V. H., & Weller, R. O. (2008) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00926.x · Cited by 665 · see citing works
Self-citation
The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?
Abbott, N. J., Pizzo, M. E., Preston, J. E., Janigro, D., & Thorne, R. G. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1812-4 · Cited by 593 · see citing works
Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
Sierra, A., Abiega, O., Shahraz, A., & Neumann, H. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00006 · Cited by 574 · see citing works
Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment
Bisgaard, T. H., Allin, K. H., Keefer, L., Ananthakrishnan, A. N., & Jess, T. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00634-6 · Cited by 572 · see citing works
What is the blood–brain barrier (not)?
Bechmann, I., Galea, I., & Perry, V. H. (2007) · Trends in Immunology · doi:10.1016/j.it.2006.11.007 · Cited by 520 · see citing works
Self-citation
Lymphatic drainage of the brain and the pathophysiology of neurological disease
Weller, R. O., Djuanda, E., Yow, H.-Y., & Carare, R. O. (2009) · Acta Neuropathologica · doi:10.1007/s00401-008-0457-0 · Cited by 488 · see citing works
The role of inflammation and the gut microbiome in depression and anxiety
Peirce, J. M., & Alviña, K. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24476 · Cited by 466 · see citing works
Macrophages at CNS interfaces: Ontogeny and function in health and disease
Kierdorf, K., Masuda, T., Jordão, M. J. C., & Prinz, M. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0201-x · Cited by 416 · see citing works
Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?
Danese, A., & J Lewis, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.198 · Cited by 393 · see citing works
Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation?
MEYER, U., FELDON, J., & DAMMANN, O. (2011) · Pediatric Research · doi:10.1203/pdr.0b013e318212c196 · Cited by 357 · see citing works
Vascular, glial, and lymphatic immune gateways of the central nervous system
Engelhardt, B., Carare, R. O., Bechmann, I., Flügel, A., Laman, J. D., & Weller, R. O. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1606-5 · Cited by 362 · see citing works
Self-citation
CNS Infection and Immune Privilege
Forrester, J. V., McMenamin, P. G., & Dando, S. J. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0070-8 · Cited by 313 · see citing works
The anatomy and immunology of vasculature in the central nervous system
Mastorakos, P., & McGavern, D. (2019) · Science Immunology · doi:10.1126/sciimmunol.aav0492 · Cited by 333 · see citing works
Microglia–blood vessel interactions: a double-edged sword in brain pathologies
Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., & Schmidt, M. H. H. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1524-y · Cited by 301 · see citing works
Advances in Meningeal Immunity
Rua, R., & McGavern, D. B. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.04.003 · Cited by 326 · see citing works
Hidden wounds? inflammatory links between childhood trauma and psychopathology
Danese, A., & Baldwin, J. R. (2017) · Annual Review of Psychology · doi:10.1146/annurev-psych-010416-044208 · Cited by 286 · see citing works
T cell responses in the central nervous system
Korn, T., & Kallies, A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.144 · Cited by 268 · see citing works
TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice
Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I., & Deller, T. (2008) · Glia · doi:10.1002/glia.20710 · Cited by 247 · see citing works
Self-citation
The blood-brain barrier, chemokines and multiple sclerosis
Holman, D. W., Klein, R. S., & Ransohoff, R. M. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.07.019 · Cited by 247 · see citing works
Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke
Lopes Pinheiro, M. A., Kooij, G., Mizee, M. R., Kamermans, A., Enzmann, G., Lyck, R., Schwaninger, M., Engelhardt, B., & de Vries, H. E. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.018 · Cited by 247 · see citing works
Temporal Changes in Cell Marker Expression and Cellular Infiltration in a Controlled Cortical Impact Model in Adult Male C57BL/6 Mice
Jin, X., Ishii, H., Bai, Z., Itokazu, T., & Yamashita, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041892 · Cited by 211 · see citing works
Microglial immune checkpoint mechanisms
Deczkowska, A., Amit, I., & Schwartz, M. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0145-x · Cited by 185 · see citing works
On phagocytes and macular degeneration
Guillonneau, X., Eandi, C. M., Paques, M., Sahel, J.-A., Sapieha, P., & Sennlaub, F. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.06.002 · Cited by 185 · see citing works
Dysregulated neuronal–microglial cross-talk during aging, stress and inflammation
Jurgens, H. A., & Johnson, R. W. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.014 · Cited by 179 · see citing works
PU.1 regulates Alzheimer’s disease-associated genes in primary human microglia
Rustenhoven, J., Smith, A. M., Smyth, L. C., Jansson, D., Scotter, E. L., Swanson, M. E. V., Aalderink, M., Coppieters, N., Narayan, P., Handley, R., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0277-1 · Cited by 155 · see citing works
Where are we? The anatomy of the murine cortical meninges revisited for intravital imaging, immunology, and clearance of waste from the brain
Coles, J. A., Myburgh, E., Brewer, J. M., & McMenamin, P. G. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.05.002 · Cited by 123 · see citing works
Infection drives meningeal engraftment by inflammatory monocytes that impairs CNS immunity
Rua, R., Lee, J. Y., Silva, A. B., Swafford, I. S., Maric, D., Johnson, K. R., & McGavern, D. B. (2019) · Nature Immunology · doi:10.1038/s41590-019-0344-y · Cited by 123 · see citing works
Ischemia–reperfusion injury in stroke: impact of the brain barriers and brain immune privilege on neutrophil function
Enzmann, G., Kargaran, S., & Engelhardt, B. (2018) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286418794184 · Cited by 119 · see citing works
Increased densities of T and B lymphocytes indicate neuroinflammation in subgroups of schizophrenia and mood disorder patients.
Schlaaff, K., Dobrowolny, H., Frodl, T., Mawrin, C., Gos, T., Steiner, J., & Bogerts, B. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.04.021 · Cited by 107 · see citing works
Central nervous system stromal cells control local CD8 + T cell responses during virus-induced neuroinflammation.
Cupovic, J., Onder, L., Gil-Cruz, C., Weiler, E., Caviezel-Firner, S., Perez-Shibayama, C., Rülicke, T., Bechmann, I., & Ludewig, B. (2016) · Immunity · doi:10.1016/j.immuni.2015.12.022 · Cited by 98 · see citing works
Self-citation
Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function
Zhang, Y., Bailey, J. T., Xu, E., Singh, K., Lavaert, M., Link, V. M., D’Souza, S., Hafiz, A., Cao, J., Cao, G., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01349-1 · Cited by 91 · see citing works
Primitive mechanisms of trauma response: an evolutionary perspective on trauma-related disorders.
Baldwin, D. V. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.06.004 · Cited by 85 · see citing works
TLR-Mediated Signal Transduction and Neurodegenerative Disorders
Adhikarla, S. V., Jha, N. K., Goswami, V. K., Sharma, A., Bhardwaj, A., Dey, A., Villa, C., Kumar, Y., & Jha, S. K. (2021) · Brain Sciences · doi:10.3390/brainsci11111373 · Cited by 50 · see citing works
Lack of Major Histocompatibility complex class I upregulation and restrictive infection by JC virus hamper detection of neurons by T lymphocytes in the central nervous system
Wüthrich, C., Batson, S., & Koralnik, I. J. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000218 · Cited by 10 · see citing works

Authors: Galea, I., Bechmann, I., & Perry, V. H.
Affiliations: University of Southampton (GB)
Goethe University Frankfurt (DE)
Corresponding author: Galea, Ian
ORCID: Galea, Ian
Bechmann, Ingo
Perry, V. Hugh
Venue: Trends in Immunology
Publisher: Elsevier BV
Published: 2007-01
Volume: 28
Issue: 1
Pages: 12-18
ISSN: 1471-4906 (ISSN-L)
DOI: 10.1016/j.it.2006.11.004
OpenAlex: W2034387476
Cited by: 768
References: 86
Citations by year: 2026: 28 · 2025: 26 · 2024: 24 · 2023: 37 · 2022: 34 · 2021: 44 · 2020: 48 · 2019: 41 · 2018: 42 · 2017: 39 · 2016: 32 · 2015: 51 · 2014: 40 · 2013: 58 · 2012: 49
FWCI: 3.67
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Immunology (publishedVersion)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (acceptedVersion)
Funders: Multiple Sclerosis Society
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: immune privilege, central nervous system, blood-brain barrier, adaptive immunity, cervical lymph nodes, immune regulation, neuroinflammation, age differences, regional brain differences
MeSH terms: Animals, Blood-Brain Barrier, Brain, Central Nervous System, Humans, Immune Tolerance, Mice, Rats

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

What is immune privilege (not)?

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks