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T‐lymphocyte entry into the central nervous system
Abstract
The entry of T‐lymphocytes into the parenchyma of the central nervous system is a critical early feature in the pathogenesis of many experimental and spontaneously occurring immune‐mediated illnesses. The physiological mechanisms controlling this entry have not been elucidated. This study reports that T‐cell entry into the rat CNS appears to be primarily dependent upon the activation state of the lymphocytes; T‐lymphoblasts enter the CNS (and all other tissues examined) in an apparently random manner while T cells not in blast phase are excluded. Antigen specificity, MHC compatibility, T‐cell phenotypce and T‐cell receptor gene usage do not appear related to the ability of cells to enter. This study demonstrates that when T‐lymphoblasts are introduced into the circulation they rapidly appear in the CNS tissue. Their concentration in the CNS reaches a peak between 9 and 12 hr, and lymphocytes which have entered, exit within 1 to 2 days. Cells capable of reacting with a CNS antigen remain in the tissue or cyclically reenter to initiate inflammation if they are able to recognize their antigen in the correct MHC context. This observation also appears to pertain to the entry of activated T cells into many other tissues, although their concentrations in these non‐CNS sites was not quantitatied.
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Citations
Cites
Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo
Hickey, W. F., & Kimura, H. (1988) · Science · doi:10.1126/science.3276004 · Cited by 1,466
Self-citation
Cited by
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906
Immune-neuro-endocrine interactions: facts and hypotheses.
BESEDOVSKY, H. O., & REY, A. D. (1996) · Endocrine Reviews · doi:10.1210/edrv-17-1-64 · Cited by 1,564
Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N., Cohen, H., Kipnis, J., & Schwartz, M. (2006) · Nature Neuroscience · doi:10.1038/nn1629 · Cited by 1,209
Reboldi, A., Coisne, C., Baumjohann, D., Benvenuto, F., Bottinelli, D., Lira, S., Uccelli, A., Lanzavecchia, A., Engelhardt, B., & Sallusto, F. (2009) · Nature Immunology · doi:10.1038/ni.1716 · Cited by 1,206
Neuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107
Tissue-Resident Memory T Cells
Schenkel, J. M., & Masopust, D. (2014) · Immunity · doi:10.1016/j.immuni.2014.12.007 · Cited by 1,059
“It was found that only effector, and notmemory, CD8+ T cells were competent to enter the small intestine, brain, or salivary gland (Hickey et al., 1991; Hofmann and Pircher, 2011; Masopust et al., 2010; Wakim et al., 2010).”
BackgroundInfiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool
Ajami, B., Bennett, J. L., Krieger, C., McNagny, K. M., & Rossi, F. M. V. (2011) · Nature Neuroscience · doi:10.1038/nn.2887 · Cited by 1,061
Babbe, H., Roers, A., Waisman, A., Lassmann, H., Goebels, N., Hohlfeld, R., Friese, M., Schröder, R., Deckert, M., Schmidt, S., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.3.393 · Cited by 951
Butovsky, O., Ziv, Y., Schwartz, A., Landa, G., Talpalar, A. E., Pluchino, S., Martino, G., & Schwartz, M. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.10.006 · Cited by 923
The Blood-Brain Barrier in Brain Homeostasis and Neurological Diseases
Weiss, N., Miller, F., Cazaubon, S., & Couraud, P.-O. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.10.022 · Cited by 731
Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity
Olmos, G., & Lladó, J. (2014) · Mediators of Inflammation · doi:10.1155/2014/861231 · Cited by 730
Cc Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis
Fife, B. T., Huffnagle, G. B., Kuziel, W. A., & Karpus, W. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.6.899 · Cited by 511
Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases
Togo, T., Akiyama, H., Iseki, E., Kondo, H., Ikeda, K., Kato, M., Oda, T., Tsuchiya, K., & Kosaka, K. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00496-9 · Cited by 481
Inflammatory processes in amyotrophic lateral sclerosis
McGeer, P. L., & McGeer, E. G. (2002) · Muscle & Nerve · doi:10.1002/mus.10191 · Cited by 470
Ridder, K., Keller, S., Dams, M., Rupp, A.-K., Schlaudraff, J., Del Turco, D., Starmann, J., Macas, J., Karpova, D., Devraj, K., et al. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001874 · Cited by 412
Modulation of immune response by head injury
Morganti-Kossmann, M. C., Satgunaseelan, L., Bye, N., & Kossmann, T. (2007) · Injury · doi:10.1016/j.injury.2007.10.005 · Cited by 412
Transforming the understanding of brain immunity
Castellani, G., Croese, T., Peralta Ramos, J. M., & Schwartz, M. (2023) · Science · doi:10.1126/science.abo7649 · Cited by 386
Dealing with danger in the CNS: the response of the immune system to injury
Gadani, S. P., Walsh, J. T., Lukens, J. R., & Kipnis, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.019 · Cited by 342
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349
Alterations of T-lymphocyte populations in Parkinson disease
Baba, Y., Kuroiwa, A., Uitti, R. J., Wszolek, Z. K., & Yamada, T. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2005.07.005 · Cited by 336
Glial cell influence on the human blood‐brain barrier
Prat, A., Biernacki, K., Wosik, K., & Antel, J. P. (2001) · Glia · doi:10.1002/glia.1104 · Cited by 334
Marchetti, L., & Engelhardt, B. (2020) · Vascular Biology · doi:10.1530/vb-19-0033 · Cited by 304
Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here
Tobin, M. K., Bonds, J. A., Minshall, R. D., Pelligrino, D. A., Testai, F. D., & Lazarov, O. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.130 · Cited by 310
Bone marrow derived elements and resident microglia in brain inflammation
Lassmann, H., Schmied, M., Vass, K., & Hickey, W. F. (1993) · Glia · doi:10.1002/glia.440070106 · Cited by 280
Self-citationT cell responses in the central nervous system
Korn, T., & Kallies, A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.144 · Cited by 268
Expression of CCR7 in multiple sclerosis: implications for CNS immunity
Kivisäkk, P., Mahad, D. J., Callahan, M. K., Sikora, K., Trebst, C., Tucky, B., Wujek, J., Ravid, R., Staugaitis, S. M., Lassmann, H., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20049 · Cited by 267
Brain borders at the central stage of neuroimmunology
Rustenhoven, J., & Kipnis, J. (2022) · Nature · doi:10.1038/s41586-022-05474-7 · Cited by 253
Kawakami, N., Nägerl, U. V., Odoardi, F., Bonhoeffer, T., Wekerle, H., & Flügel, A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050011 · Cited by 248
Piccio, L., Rossi, B., Scarpini, E., Laudanna, C., Giagulli, C., Issekutz, A. C., Vestweber, D., Butcher, E. C., & Constantin, G. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.4.1940 · Cited by 245
Greenwood, J., Heasman, S. J., Alvarez, J. I., Prat, A., Lyck, R., & Engelhardt, B. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2010.01140.x · Cited by 240
Groeschel, S., Chong, W. K., Surtees, R., & Hanefeld, F. (2006) · Neuroradiology · doi:10.1007/s00234-006-0112-1 · Cited by 230
Mast Cells Migrate from Blood to Brain
Silverman, A.-J., Sutherland, A. K., Wilhelm, M., & Silver, R. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00401.2000 · Cited by 228
Retinal microglia initiate neuroinflammation in ocular autoimmunity
Okunuki, Y., Mukai, R., Nakao, T., Tabor, S. J., Butovsky, O., Dana, R., Ksander, B. R., & Connor, K. M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820387116 · Cited by 216
Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment
Carrithers, M. D., Visintin, I., Kang, S. J., & Janeway, C. A. (2000) · Brain · doi:10.1093/brain/123.6.1092 · Cited by 220
Williams, D. W., Eugenin, E. A., Calderon, T. M., & Berman, J. W. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0811394 · Cited by 212
Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment
Singhal, G., Jaehne, E. J., Corrigan, F., & Baune, B. T. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00097 · Cited by 186
Webster, M. J., Knable, M. B., Johnston-Wilson, N., Nagata, K., Inagaki, M., & Yolken, R. H. (2001) · Brain, Behavior, and Immunity · doi:10.1006/brbi.2001.0646 · Cited by 179
Neuropathobiology of COVID-19: The Role for Glia
Tremblay, M.-E., Madore, C., Bordeleau, M., Tian, L., & Verkhratsky, A. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592214 · Cited by 159
“For example, effectors T- and B-lymphocytes enter the CNS (even when the BBB stays intact) aiming at invasive pathogens (Hickey et al., 1991; Carson et al., 2006).”
BackgroundBrain‐Specific Autoantibodies in the Plasma of Subjects with Autistic Spectrum Disorder
CABANLIT, M., WILLS, S., GOINES, P., ASHWOOD, P., & VAN DE WATER, J. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1381.010 · Cited by 157
Mechanisms of leukocyte migration across the blood-retina barrier
Crane, I. J., & Liversidge, J. (2008) · Seminars in Immunopathology · doi:10.1007/s00281-008-0106-7 · Cited by 152
Beyond the gut: decoding the gut–immune–brain axis in health and disease
Park, J. C., Chang, L., Kwon, H.-K., & Im, S.-H. (2025) · Cellular & Molecular Immunology · doi:10.1038/s41423-025-01333-3 · Cited by 149
Non-neuronal cells in amyotrophic lateral sclerosis — from pathogenesis to biomarkers
Vahsen, B. F., Gray, E., Thompson, A. G., Ansorge, O., Anthony, D. C., Cowley, S. A., Talbot, K., & Turner, M. R. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00487-8 · Cited by 147
Nagai, M., Yamano, Y., Brennan, M. B., Mora, C. A., & Jacobson, S. (2001) · Annals of Neurology · doi:10.1002/ana.10065 · Cited by 144
IL-4-Induced Selective Clearance of Oligomeric β-Amyloid Peptide1–42 by Rat Primary Type 2 Microglia
Shimizu, E., Kawahara, K., Kajizono, M., Sawada, M., & Nakayama, H. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.6503 · Cited by 143
Turnover of Rat Brain Perivascular Cells
Bechmann, I., Kwidzinski, E., Kovac, A. D., Simbürger, E., Horvath, T., Gimsa, U., Dirnagl, U., Priller, J., & Nitsch, R. (2001) · Experimental Neurology · doi:10.1006/exnr.2000.7618 · Cited by 134
CNS: Not an immunoprivilaged site anymore but a virtual secondary lymphoid organ
Negi, N., & Das, B. K. (2018) · International Reviews of Immunology · doi:10.1080/08830185.2017.1357719 · Cited by 123
Monsonego, A., Imitola, J., Zota, V., Oida, T., & Weiner, H. L. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.5.2216 · Cited by 91
Pender, M. P. (1999) · Immunology & Cell Biology · doi:10.1046/j.1440-1711.1999.00818.x · Cited by 77
MHC class II exacerbates demyelination in vivo independently of T cells
Hiremath, M. M., Chen, V. S., Suzuki, K., Ting, J. P.-Y., & Matsushima, G. K. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.06.034 · Cited by 77
Fingolimod: A Disease-Modifier Drug in a Mouse Model of Amyotrophic Lateral Sclerosis
Potenza, R. L., De Simone, R., Armida, M., Mazziotti, V., Pèzzola, A., Popoli, P., & Minghetti, L. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0462-2 · Cited by 69
Macrophages and microglia in central nervous system injury: are they helpful or harmful?
Schwartz, M. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200304000-00001 · Cited by 207
Neurons under viral attack: Victims or warriors?
Chakraborty, S., Nazmi, A., Dutta, K., & Basu, A. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.02.016 · Cited by 42
Potential importance of B cells in aging and aging-associated neurodegenerative diseases
Biragyn, A., Aliseychik, M., & Rogaev, E. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-016-0615-8 · Cited by 25
Metadata
- Authors
- Hickey, W. F., Hsu, B. L., & Kimura, H.
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 1991-02
- Volume
- 28
- Issue
- 2
- Pages
- 254-260
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2017605183
- Cited by
- 1,177
- References
- 1
- FWCI
- 22.93
- Type
- journal article
- Language
- en
- Open access
- closed
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