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Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis.
Abstract
Relapsing experimental autoimmune encephalomyelitis (R-EAE) can be induced in SJL/J mice by immunization with spinal cord homogenate and adjuvant. The specific Ag(s) responsible for acute disease and subsequent relapses in this model is unknown. Myelin basic protein (BP), an encephalitogenic peptide of BP (BP 87-99), and proteolipid protein (PLP) can each induce R-EAE in SJL/J mice, and a peptide of PLP (PLP 139-151) has been reported to induce acute EAE. To determine the encephalitogens in cord-immunized mice with R-EAE, the in vitro proliferative responses of lymph node cells (LNC) and central nervous system mononuclear cells to BP, BP peptides, and PLP peptides were examined during acute EAE and during relapses. LNC responded only to PLP peptides 139-151 and 141-151 and did not respond to BP or its peptides during acute or chronic disease. Central nervous system mononuclear cells also preferentially responded to PLP 139-151 and 141-151 during acute and relapsing disease. A PLP 139-151 peptide-specific Th cell line was selected from LNC of cord-immunized donors. Five million peptide-specific line cells transferred severe relapsing demyelinating EAE to naive recipients. We conclude that PLP peptide 139-151 is the major encephalitogen for R-EAE in cord-immunized SJL/J mice. We demonstrate for the first time that Th cells specific for this peptide are sufficient to transfer relapsing demyelinating EAE. The predominance of a PLP immune response rather than a BP response in SJL/J mice suggests that genetic background may determine the predominant myelin Ag response in human demyelinating diseases such as multiple sclerosis.
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“We also studied therapeutic efficacy in the proteolipid protein (PLP)-induced acute mouse EAE, a routinely used model for the autoimmune inflammatory neurodegenerative disease multiple sclerosis [39], [40], in which the involvement of inflammation in the brain enhance the permeability of this difficult to reach organ.”
From Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids (2011) · cites this paper as [40]
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“by an irregular RR phase (McRae et al., 1995; Tsunoda and Fujinami, 1996; Whitham et al., 1991).”
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“SJL mice immunized with whole-spinal cord homogenate, which contains all myelin antigens, respond selectively to PLP 139–151 (12).”
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“Degrees of hind limb and forelimb weaknesses were assessed as described below and as previously outlined (Whitham et al., 1991); flaccid tail—clinical severity score of 1; difficulty in righting after being flipped onto their backs—clinical severity score of 2; apparent hind limb weakness and not able to right themsel…”
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Development of IL-17A-associated autoimmunity
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Metadata
- Authors
- Whitham, R. H., Bourdette, D. N., Hashim, G. A., Herndon, R. M., Ilg, R. C., Vandenbark, A. A., & Offner, H.
- Affiliations
- Veterans Health Administration (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1991-01-01
- Volume
- 146
- Issue
- 1
- Pages
- 101-107
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1562022567
- Cited by
- 130
- References
- 0
- Citations by year
- 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns021466-05)
- National Institute of Neurological Disorders and Stroke (NS23444, NS23221, NS 21466, R01NS023444, R01NS023221)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- proteolipid protein, myelin basic protein, SJL/J mice, T cell transfer, multiple sclerosis, genetic background, demyelinating disease
- MeSH terms
- Animals, Brain, Cell Line, Encephalomyelitis, Autoimmune, Experimental, Female, T-Lymphocytes, Helper-Inducer, Immunization, Passive, Leukocytes, Mononuclear, Lymph Nodes, Lymphocyte Activation, Mice, Inbred Strains, Myelin Proteins, Peptide Fragments, Spinal Cord, Time Factors, Myelin Proteolipid Protein, Mice
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