In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells

• Published in: PLoS pathogens Vol. 6; no. 1; p. e1000748
• Main Authors: Wong, Joseph K, Strain, Matthew C, Porrata, Rodin, Reay, Elizabeth, Sankaran-Walters, Sumathi, Ignacio, Caroline C, Russell, Theresa, Pillai, Satish K, Looney, David J, Dandekar, Satya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-01-2010; Public Library of Science (PLoS)
• Subjects: Animals; Anti-Retroviral Agents - pharmacology; Antiretroviral drugs; CD8-Positive T-Lymphocytes - immunology; Control; Cytotoxicity; Evolution; Experiments; Gene Expression; Gene Products, gag - biosynthesis; Gene Products, gag - immunology; Gene Products, nef - biosynthesis; Gene Products, nef - immunology; Health aspects; HIV; HIV infection; Human immunodeficiency virus; Immune response; Immune system; Macaca mulatta; Models, Theoretical; Physiological aspects; Plasma; Risk factors; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - drug effects; Simian Immunodeficiency Virus - immunology; T cells; T-Lymphocytes, Cytotoxic - immunology; Viral Load - drug effects; Viremia - immunology; Virology/Animal Models of Infection; Virology/Immune Evasion; Virology/Immunodeficiency Viruses; United States; Models, Theoretical; Gene Expression; Viremia; Anti-Retroviral Agents; Gene Products, gag; Macaca mulatta; T-Lymphocytes, Cytotoxic; Gene Products, nef; Viral Load; CD8-Positive T-Lymphocytes; Animals; Simian Acquired Immunodeficiency Syndrome; Simian immunodeficiency virus
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000748

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.