Title
αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic
Author
Wang, C.
Chou, Y.K.
Rich, C.M.
Link, J.M.
Afentoulis, M.E.
van Noort, J.M.
Wawrousek, E.F.
Offner, H.
van den Bark, A.A.
TNO Kwaliteit van Leven
Publication year
2006
Abstract
Alpha B-crystallin (αB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for αB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained αB-knockout (αB-KO) mice in H-2b background that lack immune tolerance to αB protein, and thus are capable of developing αB-specific T cells that could be tested for encephalitogenic activity after transfer into αB-expressing wild type (WT) mice. We found that T cell lines from spleens of αB protein-immunized αB-KO mice proliferated strongly to αB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such αB-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, αB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of αB message in the CNS at the time of transfer. These results suggest that αB-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of αB. © 2006 Elsevier B.V. All rights reserved. Chemicals / CAS: crystallin, 11046-99-4; encephalitogenic protein, 29705-91-7; alpha-Crystallin B Chain; Glycoproteins; myelin oligodendrocyte glycoprotein (35-55); Peptide Fragments
Subject
EAE/MS
Knockout mice
T cells
Tolerance
Alpha B crystallin
Amino acid derivative
Crystallin
Cytokine
Encephalitogenic protein
Heat shock protein
Methionylglutamylvalylglycyltryptophyltyrosylarginylserylprolyl Phenylalanylserylarginylvalylvalylhistidylleucyltyrosylarginylasparaginylglycyl lysine
Unclassified drug
Alpha crystallin
Glycoprotein
Myelin oligodendrocyte glycoprotein (35 55)
Peptide fragment
Allergic encephalomyelitis
Animal cell
Animal experiment
Animal model
Animal tissue
CD4+ T lymphocyte
Cell line
Cell proliferation
Central nervous system
Controlled study
Cytokine release
Disease severity
Immunization
Immunocompetence
Immunological tolerance
Mouse
Multiple sclerosis
Nonhuman
Nucleotide sequence
Protein expression
Protein function
Th1 cell
Genetics
Lmmunology
Lymph node
Molecular genetics
Mouse mutant
Physiology
Reverse transcription polymerase chain reaction
Alpha-Crystallin B Chain
Amino Acid Sequence
Animals
Encephalomyelitis, Autoimmune, Experimental
Glycoproteins
Lymph Nodes
Lymphocyte Activation
Mice
Mice, Knockout
Molecular Sequence Data
Peptide Fragments
Reverse Transcriptase Polymerase Chain Reaction
Spleen
T-Lymphocytes
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DOI
https://doi.org/10.1016/j.jneuroim.2006.04.010
TNO identifier
239345
ISSN
0165-5728
Source
Journal of Neuroimmunology, 176 (1-2), 51-62
Document type
article