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

Chunhe Wang, Yuan K. Chou, Cathleen M. Rich, Jason M. Link, Michael E. Afentoulis, Johannes M. van Noort, Eric F. Wawrousek, Halina Offner, Arthur A. Vandenbark

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)51-62
Number of pages12
JournalJournal of Neuroimmunology
Volume176
Issue number1-2
DOIs
StatePublished - Jul 2006

Keywords

  • EAE/MS
  • Knockout mice
  • T cells
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic'. Together they form a unique fingerprint.

  • Cite this