T- and B-cell nonresponsiveness to self-alphaB-crystallin in SJL mice prevents the induction of experimental allergic encephalomyelitis.
The myelin-associated stress protein alphaB-crystallin triggers strong proliferative responses and IFN-gamma production by human T cells and it is considered a candidate autoantigen in multiple sclerosis. In this study we examined the capacity of alphaB-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 alphaB-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-alphaB-crystallin. Also, immunization with self-alphaB-crystallin did not lead to any antibody response in SJL mice while bovine alphaB-crystallin triggered clear antibody responses within 1 week. Immunizations with alphaB-crystallin-derived peptides led to the activation of IL-4-producing Th2 cells and only a few IFN-gamma-producing Th1 cells. Peptide-specific T cells showed no cross-reactivity against whole alphaB-crystallin. The inability of SJL mice to mount proinflammatory T-cell responses against self-alphaB-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 alphaB-crystallin in both primary and secondary lymphoid organs in SJL mice, which is seen in other mammals as well, but not in humans.
van Stipdonk
M J
MJ
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, 2301 CE, The Netherlands.
Willems
A A
AA
Verbeek
R
R
Boog
C J
CJ
van Noort
J M
JM
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002417:Cattle; D003459:Crystallins / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009186:Myelin Sheath / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D003459:Crystallins; D006183:H-2 Antigens; D009419:Nerve Tissue Proteins; D015847:Interleukin-4; D007371:Interferon-gamma