The functional avidity of virus-specific CD8 super(+) T cells is down-modulated in Borna disease virus-induced immunopathology of the central nervous system

• Published in: European Journal of Immunology 2005-01, Vol.35 (2), p.487-497
• Main Authors: Engelhardt, Karin R, Richter, Kirsten, Baur, Karen, Staeheli, Peter, Hausmann, Juergen
• Format: Article
• Language: English
• Subjects: Borna disease virus
• ISSN: 0014-2980; 1365-2567
• DOI: 10.1002/eji.200425232

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 super(+) 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 super(+) T cells. We found that on average approximately 30% of the ex vivo analyzed CD8 super(+) T cells in the CNS of diseased mice were specific for TELEISSI. Unexpectedly, the frequency of tetramer-reactive brain-derived CD8 super(+) T cells doubled following overnight culture in the absence of antigen. The majority of CD8 super(+) T cells showed enhanced tetramer binding without up-regulation of T cell receptor surface expression. The frequency of IFN-[ggr]-secreting CD8 super(+) 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 super(+) T cells was down-modulated in vivo. Thus, quantification of tissue- infiltrating CD8 super(+) T cells by the tetramer technique must be interpreted with caution as it may underestimate the real frequency of antigen-specific CD8 super(+) T cells.