title: T cell exhaustion during persistent viral infections.
abstract: Although robust and highly effective anti-viral T cells contribute to the clearance of many acute infections, viral persistence is associated with the development of functionally inferior, exhausted, T cell responses. Exhaustion develops in a step-wise and progressive manner, ranges in severity, and can culminate in the deletion of the anti-viral T cells. This disarming of the response is consequential as it compromises viral control and potentially serves to dampen immune-mediated damage. Exhausted T cells are unable to elaborate typical anti-viral effector functions. They are characterized by the sustained upregulation of inhibitory receptors and display a gene expression profile that distinguishes them from prototypic effector and memory T cell populations. In this review we discuss the properties of exhausted T cells; the virological and immunological conditions that favor their development; the cellular and molecular signals that sustain the exhausted state; and strategies for preventing and reversing exhaustion to favor viral control.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Kahan
authors.affiliation: Institute for Immunology and Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: wherry@mail.med.upenn.edu.
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: azajac@uab.edu.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Zajac
mesh_terms: D000818:Animals; D002908:Chronic Disease; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology* / Q000821:virology*
keywords: Cytokines; Immunity; Inhibitory receptors; Persistent infections; T cell exhaustion