title: CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion.
abstract: Repetitive Ag encounter, coupled with dynamic changes in Ag density and inflammation, imparts phenotypic and functional heterogeneity to memory virus-specific CD8 T cells in persistently infected hosts. For herpesvirus infections, which cycle between latency and reactivation, recent studies demonstrate that virus-specific T cell memory is predominantly derived from naive precursors recruited during acute infection. Whether functional memory T cells to viruses that persist in a nonlatent, low-level infectious state (smoldering infection) originate from acute infection-recruited naive T cells is not known. Using mouse polyomavirus (MPyV) infection, we previously showed that virus-specific CD8 T cells in persistently infected mice are stably maintained and functionally competent; however, a sizeable fraction of these memory T cells are short-lived. Further, we found that naive anti-MPyV CD8 T cells are primed de novo during persistent infection and contribute to maintenance of the virus-specific CD8 T cell population and its phenotypic heterogeneity. Using a new MPyV-specific TCR-transgenic system, we now demonstrate that virus-specific CD8 T cells recruited during persistent infection possess multicytokine effector function, have strong replication potential, express a phenotype profile indicative of authentic memory capability, and are stably maintained. In contrast, CD8 T cells recruited early in MPyV infection express phenotypic and functional attributes of clonal exhaustion, including attrition from the memory pool. These findings indicate that naive virus-specific CD8 T cells recruited during persistent infection contribute to preservation of functional memory against a smoldering viral infection.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jarad J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pack
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Frost
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Albrecht
authors.forename: Annette
authors.initials: A
authors.lastname: Hadley
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Hofstetter
authors.forename: Satvir S
authors.initials: SS
authors.lastname: Tevethia
authors.forename: Todd D
authors.initials: TD
authors.lastname: Schell
authors.forename: Aron E
authors.initials: AE
authors.lastname: Lukacher
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000235:genetics / Q000276:immunology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology*