T- and B-cell nonresponsiveness to self-αB-crystallin in SJL mice prevents the induction of experimental allergic encephalomyelitis
article
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
Topics
AntigensRodentsToleranceAlpha crystallinBeta crystallinPeptideActive immunizationAdoptive transferAllergic encephalomyelitisAnimal cellAnimal experimentAnimal modelAntibody responseAutoimmunityCell lineCell proliferationCytokine productionImmunological toleranceImmunopathogenesisLymphocyte functionLymphoid organNonhumanProtein expressionAdoptive TransferAnimalsAutoimmunityB-LymphocytesCattleCrystallinsEncephalomyelitis, Autoimmune, ExperimentalFemaleH-2 AntigensImmune ToleranceInterferon Type IIInterleukin-4LymphocytesLymphoid TissueMiceMice, Inbred StrainsMyelin SheathNerve Tissue ProteinsSpecies SpecificityT-LymphocytesVaccination
TNO Identifier
235662
ISSN
00088749
Source
Cellular Immunology, 204(2), pp. 128-134.
Pages
128-134
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