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Cited by 862Multiple Sclerosis Research StudiesImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis

Greter, Melanie, Heppner, Frank L, Lemos, Maria P, Odermatt, Bernhard M, Goebels, Norbert, Laufer, Terri, Noelle, Randolph J, Becher, Burkhard·2005·Nature Medicine
DOI 10.1038/nm1197
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Abstract

Immunization with myelin antigens leads to the development of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. The disease can also be induced by the transfer of encephalitogenic CD4+ T helper (T(H)) lymphocytes into naive mice. These T cells need to re-encounter their cognate antigen in the context of major histocompatibility complex (MHC) class II-bearing antigen-presenting cells (APCs) in order to recognize their target. The cell type and location of the APC mediating T-cell entry into the central nervous system (CNS) remain unknown. Here, we show that APCs of the lymphoreticular system and of the CNS parenchyma are dispensable for the immune invasion of the CNS. We also describe that a discrete population of vessel-associated dendritic cells (DCs) is present in human brain tissue. In mice, CD11c+ DCs alone are sufficient to present antigen in vivo to primed myelin-reactive T cells in order to mediate CNS inflammation and clinical disease development.

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Crossref · 10.1038/nm1197

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42 of 42 references verified0 citation errors · 0 not checkable

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  • Definitive evidence of a non-redundant role for monocyte-derived APC in activating autoreactive T cells is lacking.

    “As both peripherally-derived and CNS-resident myeloid cells have been implicated in antigen presentation to autoreactive T cells, definitive evidence of a non-redundant role for monocyte-derived APC in activating autoreactive T cells is lacking.”

    From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [136]

  • Immune surveillance and the initiation of CNS immune responses is dependent on antigen-presenting cells that reside alongside important barriers such as perivascular spaces, leptomeningeal vessels, the choroid plexus, and the subarachnoid space.

    “Immune surveillance and the initiation of CNS immune responses is dependent on antigen-presenting cells (APCs) that reside alongside important barriers such as perivascular spaces, leptomeningeal vessels, the choroid plexus, and the subarachnoid space (65-68).”

    From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [65]

  • Activated T cells need to recognize cognate antigen presented by perivascular APCs to enter the CNS parenchyma; otherwise, they undergo apoptosis or reenter the circulation.

    “In addition, activated T cells need to recognize cognate antigen presented by perivascular APCs to enter the CNS parenchyma (65, 84); otherwise, they undergo apoptosis or reenter the circulation.”

    From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [65]

  • Upon extravasation, autoreactive T cells interact with peptide-MHC II-bearing APCs in perivascular spaces, triggering up-regulation of chemokines that recruit myeloid cells and release of TNFα that increases production of MMP-2 and MMP-9 by resident and recruited myeloid cells.

    “Upon extravasation, the autoreactive T cells interact with peptide–major histocompatibility complex (MHC) II–bearing APCs (such as DCs) in the perivascular spaces, triggering up-regulation of chemokines that recruit myeloid cells and release of TNFα that increases production of metalloproteinases MMP-2 and MMP-9 by resident and recruited myeloid cells (Fig. 4) (65, 67, 84, 119, 120).”

    From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [65]

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Authors
Greter, M., Heppner, F. L., Lemos, M. P., Odermatt, B. M., Goebels, N., Laufer, T., Noelle, R. J., & Becher, B.
Affiliations
  • University Hospital Zurich (CH)
  • University of Pennsylvania (US)
  • Dartmouth College (US)
Corresponding author
Becher, Burkhard
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2005-02-27
Volume
11
Issue
3
Pages
328-334
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm1197
OpenAlex
W2053313675
Cited by
862
References
42
Citations by year
2026: 8 · 2025: 26 · 2024: 29 · 2023: 25 · 2022: 30 · 2021: 36 · 2020: 38 · 2019: 34 · 2018: 33 · 2017: 41 · 2016: 36 · 2015: 40 · 2014: 44 · 2013: 48 · 2012: 59
FWCI
43.27
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI049580, AI49580)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
dendritic cells, multiple sclerosis, experimental autoimmune encephalomyelitis, antigen-presenting cells, myelin-specific T cells, CD4+ T helper cells, CD11c+ dendritic cells, reticuloendothelial system, MHC class II, neuroinflammation
MeSH terms
Animals, Antigen-Presenting Cells, Brain, Cell Movement, Chimera, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, Genes, MHC Class II, T-Lymphocytes, Helper-Inducer, Humans, Multiple Sclerosis, Myelin Sheath, Antigen Presentation, CD11c Antigen, Mice

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