title: The functional avidity of virus-specific CD8+ T cells is down-modulated in Borna disease virus-induced immunopathology of the central nervous system.
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.
authors.affiliation: Department of Virology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
authors.forename: Karin R
authors.initials: KR
authors.lastname: Engelhardt
authors.forename: Kirsten
authors.initials: K
authors.lastname: Richter
authors.forename: Karen
authors.initials: K
authors.lastname: Baur
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hausmann
mesh_terms: D000818:Animals; D001890:Borna Disease / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D001891:Borna disease virus / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015536:Down-Regulation; D006183:H-2 Antigens / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D010455:Peptides; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma