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αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic

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Author: Wang, C. · Chou, Y.K. · Rich, C.M. · Link, J.M. · Afentoulis, M.E. · Noort, J.M. van · Wawrousek, E.F. · Offner, H. · Bark, A.A. van den
Institution: TNO Kwaliteit van Leven
Source:Journal of Neuroimmunology, 1-2, 176, 51-62
Identifier: 239345
doi: doi:10.1016/j.jneuroim.2006.04.010
Keywords: 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


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