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T- and B-cell nonresponsiveness to self-αB-crystallin in SJL mice prevents the induction of experimental allergic encephalomyelitis

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Author: Stipdonk, M.J.B. van · Willems, A.A. · Verbeek, R. · Boog, C.J.P. · Noort, J.M. van
Type:article
Date:2000
Institution: TNO Preventie en Gezondheid
Source:Cellular Immunology, 2, 204, 128-134
Identifier: 235662
doi: doi:10.1006/cimm.2000.1698
Keywords: 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

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