T- and B-cell nonresponsiveness to self-αB-crystallin in SJL mice prevents the induction of experimental allergic encephalomyelitis
van Stipdonk, M.J.B.
van Noort, J.M.
TNO Preventie en Gezondheid
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
To reference this document use:
Encephalomyelitis, Autoimmune, Experimental
Interferon Type II
Mice, Inbred Strains
Nerve Tissue Proteins
Cellular Immunology, 204 (2), 128-134