The functional avidity of virus-specific CD8+ T cells is down-modulated in Borna disease virus-induced immunopathology of the central nervous system |
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Authors: | Engelhardt Karin R Richter Kirsten Baur Karen Staeheli Peter Hausmann Jürgen |
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Institution: | Department of Virology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany. |
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Abstract: | Borna disease virus (BDV) infection of the central nervous system (CNS) leads to severe neurological symptoms in susceptible MRL mice. The disease is mainly mediated by CD8+ T cells specific for the immunodominant epitope TELEISSI in the BDV nucleoprotein. In this study, TELEISSI/MHC class I tetramers were used to directly visualize antigen-specific CD8+ T cells. We found that on average approximately 30% of the ex vivo analyzed CD8+ T cells in the CNS of diseased mice were specific for TELEISSI. Unexpectedly, the frequency of tetramer-reactive brain-derived CD8+ T cells doubled following overnight culture in the absence of antigen. The majority of CD8+ T cells showed enhanced tetramer binding without up-regulation of T cell receptor surface expression. The frequency of IFN-gamma-secreting CD8+ T cells after antigen-specific stimulation was higher in overnight cultures than in freshly isolated BDV-specific brain lymphocytes, and enhanced tetramer binding correlated with elevated sensitivity to lower levels of peptide antigen in cytotoxicity assays. These results indicate that the functional avidity of virus-specific CD8+ T cells was down-modulated in vivo. Thus, quantification of tissue-infiltrating CD8+ T cells by the tetramer technique must be interpreted with caution as it may underestimate the real frequency of antigen-specific CD8+ T cells. |
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Keywords: | MHC class?I tetramer Virus Brain CD8+ T?cells Functional avidity |
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