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

Abstract

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.

• Authors: M J van Stipdonk, A A Willems, R Verbeek, C J Boog, J M van Noort
• Journal: Cellular immunology (Cell Immunol) Vol. 204 Issue 2 Pg. 128-34 (Sep 15 2000) ISSN: 0008-8749 [Print] Netherlands
• PMID: 11069720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Crystallins
• H-2 Antigens
• Nerve Tissue Proteins
• Interleukin-4
• Interferon-gamma

Topics

• Adoptive Transfer
• Animals
• Autoimmunity
• B-Lymphocytes (immunology)
• Cattle
• Crystallins (immunology)
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Female
• H-2 Antigens
• Immune Tolerance
• Interferon-gamma (analysis)
• Interleukin-4 (analysis)
• Lymphocytes (immunology)
• Lymphoid Tissue (immunology)
• Mice
• Mice, Inbred Strains
• Myelin Sheath (immunology)
• Nerve Tissue Proteins (immunology)
• Species Specificity
• T-Lymphocytes (immunology)
• Vaccination