title: In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
abstract: The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Strain
authors.forename: Rodin
authors.initials: R
authors.lastname: Porrata
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Reay
authors.forename: Sumathi
authors.initials: S
authors.lastname: Sankaran-Walters
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Ignacio
authors.forename: Theresa
authors.initials: T
authors.lastname: Russell
authors.forename: Satish K
authors.initials: SK
authors.lastname: Pillai
authors.forename: David J
authors.initials: DJ
authors.lastname: Looney
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015870:Gene Expression; D015683:Gene Products, gag / Q000096:biosynthesis / Q000276:immunology; D015693:Gene Products, nef / Q000096:biosynthesis / Q000276:immunology; D008253:Macaca mulatta; D008962:Models, Theoretical; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D015683:Gene Products, gag; D015693:Gene Products, nef