title: Immune-surveillance through exhausted effector T-cells.
abstract: Pathogens such as the human immunodeficiency virus (HIV), the hepatitis B and C virus (HBV, HCV) and certain strains of the rodent lymphocytic choriomeningitis virus (LCMV) establish a state of persisting viral replication. This occurs besides strong adoptive immune responses and the induction of large numbers of activated pathogen-specific T-cells. The failure of the immune system to clear these viruses is typically attributed to a loss of effector T-cell function-a phenomenon referred to as T-cell exhaustion. Though largely accepted, this loss of function concept is being more and more challenged by comprehensive clinical and experimental observations which highlight that T-cells in chronic infections are more functional than previously considered. Here, we highlight examples that demonstrate that such T-cells mediate a profound form of immune-surveillance. We also briefly discuss the opportunities and limitations of employing 'exhausted' T-cells for therapeutic purposes.
authors.affiliation: Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University Munich, Freising, Germany. Electronic address: dietmar.zehn@chuv.ch.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.affiliation: Department of Cellular and Molecular Medicine, UC San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0377, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Utzschneider
authors.affiliation: Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002908:Chronic Disease; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D064789:Immunity, Heterologous; D007156:Immunologic Memory; D007157:Immunologic Surveillance; D056747:Immunomodulation; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism / Q000821:virology