title: CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells.
abstract: While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Emi
authors.initials: E
authors.lastname: Shudo
authors.forename: Alex M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Engram
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Benton
authors.initials: B
authors.lastname: Lawson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: James
authors.initials: J
authors.lastname: Else
authors.forename: Ivona
authors.initials: I
authors.lastname: Pandrea
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.forename: Joern E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: Ruy M
authors.initials: RM
authors.lastname: Ribeiro
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008962:Models, Theoretical; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
chemical_list: D018925:Chemokines