CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells

• Published in: PLoS pathogens Vol. 6; no. 1; p. e1000747
• Main Authors: Klatt, Nichole R, Shudo, Emi, Ortiz, Alex M, Engram, Jessica C, Paiardini, Mirko, Lawson, Benton, Miller, Michael D, Else, James, Pandrea, Ivona, Estes, Jacob D, Apetrei, Cristian, Schmitz, Joern E, Ribeiro, Ruy M, Perelson, Alan S, Silvestri, Guido
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2010; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Animals; BASIC BIOLOGICAL SCIENCES; Care and treatment; Causes of; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Chemokines - blood; Control; Cytotoxicity, Immunologic; Health aspects; HIV; HIV infection; Human immunodeficiency virus; Immune system; Immunology; Immunology/Immune Response; Immunology/Leukocyte Activation; Infections; Infectious Diseases; Infectious Diseases/HIV Infection and AIDS; Infectious Diseases/Viral Infections; Lymphocyte Activation - immunology; Lymphocytes; Macaca mulatta; Microbiology; Microbiology/Parasitology; Models, Theoretical; Parasitology; Pathology; Pathology/Immunology; Pathology/Pathophysiology; Physiological aspects; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - physiology; T cells; Viral Load - immunology; Virology; Virus Replication - immunology; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000747

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.