Induction of EAE by T cells specific for alpha B-crystallin depends on prior viral infection in the CNS

Induction of EAE by T cells specific for alpha B-crystallin depends on prior viral infection in the CNS

Verbeek, R.
van Dongen, H.
Wawrousek, E.F.
Amor, S.
van Noort, J.M.
TNO Kwaliteit van Leven TNO Defensie en Veiligheid

2007

While myelin-reactive T cells are widely believed to play a pathogenic role in multiple sclerosis (MS), no substantial differences appear to exist in T-cell responses to myelin antigens between MS patients and healthy subjects. As an example, indistinguishable peripheral T-cell responses and serum antibody levels have been found in MS patients and healthy controls to alpha B-crystallin, a dominant antigen in MS-affected brain myelin. This suggests that additional factors are relevant in allowing myelin-reactive T cells to become pathogenic. In this study, we examined whether the inflammatory state of the CNS is relevant to the pathogenicity of alpha B-crystallin-specific T cells in mice. In normal mice, T-cell responses against alpha B-crystallin are limited by robust immunological tolerance. Reactive T cells were therefore generated in alpha B-crystallin-deficient mice, and these T cells were transferred into C57BL/6 recipients. While such a transfer in itself never induced any clinical signs of experimental autoimmune encephalomyelitis (EAE) in healthy recipient mice, acute EAE could be induced in animals that had been infected 7 days before with the avirulent A7(74) strain of Semliki Forest virus (SFV). SFV infection alone did not induce clinical disease, nor did it alter the expression levels of the target antigen. Our findings indicate that at least in mice, alpha B-crystallin-specific T cells can trigger EAE but only when prior viral infection has induced an inflammatory state in the CNS that helps recruit and activate T cells. © 2007 Oxford University Press.

Biology
Biomedical Research
alpha crystallin
myelin
allergic encephalomyelitis
animal cell
animal experiment
animal model
antigen expression
article
brain infection
cell specificity
controlled study
encephalitis
immune response
immunological tolerance
lymphocyte transfer
mouse
multiple sclerosis
nonhuman
pathogenicity
priority journal
recipient
Semliki Forest alphavirus
T lymphocyte
T lymphocyte activation
virus infection
virus strain
virus virulence
Adoptive Transfer
alpha-Crystallin B Chain
Alphavirus Infections
Animals
Cells, Cultured
Central Nervous System Viral Diseases
Encephalomyelitis, Autoimmune, Experimental
Immune Tolerance
Inflammation Mediators
Lymphocyte Activation
Mice
Mice, Biozzi
Mice, Inbred C57BL
Mice, Knockout
Semliki forest virus
Spinal Cord
T-Lymphocytes
Time Factors

http://resolver.tudelft.nl/uuid:a6cc8901-cbde-4314-83be-9a2e4e08ae83

https://doi.org/10.1093/intimm/dxl144

239866

0953-8178

International Immunology, 19 (3), 277-285

article