Title
T- and B-cell nonresponsiveness to self-αB-crystallin in SJL mice prevents the induction of experimental allergic encephalomyelitis
Author
van Stipdonk, M.J.B.
Willems, A.A.
Verbeek, R.
Boog, C.J.P.
van Noort, J.M.
TNO Preventie en Gezondheid
Publication year
2000
Abstract
The myelin-associated stress protein αB-crystallin triggers strong proliferative responses and IFN-γ production by human T cells and it is considered a candidate autoantigen in multiple sclerosis. In this study we examined the capacity of αB-crystallin or peptides derived thereof to induce experimental autoimmune encephalomyelitis (EAE) in SJL mice. Despite extensive efforts to induce EAE using active immunization with whole αB-crystallin, using adoptive transfer of lymphocytes or using peptide immunizations, no clinical or histological signs of EAE could be induced. SJL mice were unable to mount proliferative T-cell responses in vitro or delayed-type hypersensitivity responses in vivo to self-αB-crystallin. Also, immunization with self-αB-crystallin did not lead to any antibody response in SJL mice while bovine αB-crystallin triggered clear antibody responses within 1 week. Immunizations with αB-crystallin-derived peptides led to the activation of IL-4-producing Th2 cells and only a few IFN-γ-producing Th1 cells. Peptide-specific T cells showed no cross-reactivity against whole αB-crystallin. The inability of SJL mice to mount proinflammatory T-cell responses against self-αB-crystallin readily explains the lack of EAE induction by immunization with whole protein or peptides derived from it. T- and B-cell nonresponsiveness is associated with constitutive expression of full-length αB-crystallin in both primary and secondary lymphoid organs in SJL mice, which is seen in other mammals as well, but not in humans. (C) 2000 Academic Press. Chemicals/CAS: Crystallins; H-2 Antigens; Interferon Type II, 82115-62-6; Interleukin-4, 207137-56-2; Nerve Tissue Proteins
Subject
Health
Antigens
Rodents
Tolerance
Alpha crystallin
Beta crystallin
Peptide
Active immunization
Adoptive transfer
Allergic encephalomyelitis
Animal cell
Animal experiment
Animal model
Antibody response
Autoimmunity
Cell line
Cell proliferation
Cytokine production
Immunological tolerance
Immunopathogenesis
Lymphocyte function
Lymphoid organ
Nonhuman
Protein expression
Adoptive Transfer
Animals
Autoimmunity
B-Lymphocytes
Cattle
Crystallins
Encephalomyelitis, Autoimmune, Experimental
Female
H-2 Antigens
Immune Tolerance
Interferon Type II
Interleukin-4
Lymphocytes
Lymphoid Tissue
Mice
Mice, Inbred Strains
Myelin Sheath
Nerve Tissue Proteins
Species Specificity
T-Lymphocytes
Vaccination
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DOI
https://doi.org/10.1006/cimm.2000.1698
TNO identifier
235662
ISSN
0008-8749
Source
Cellular Immunology, 204 (2), 128-134
Document type
article