title: CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy.
abstract: Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8(+) lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8-32 week) ART, depletion of CD8(+) lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8(+) T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4(+) T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8(+) T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Cartwright
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Spicer
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: S Abigail
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Fast
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Paganini
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Benton O
authors.initials: BO
authors.lastname: Lawson
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Melon
authors.initials: M
authors.lastname: Nega
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA 30329, USA.
authors.forename: Kirk
authors.initials: K
authors.lastname: Easley
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Joern E
authors.initials: JE
authors.lastname: Schmitz
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Chahroudi
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Vanderford
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Electronic address: gsilves@emory.edu.
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005260:Female; D008212:Lymphocyte Depletion / Q000379:methods; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D019562:Viral Load / Q000187:drug effects / Q000276:immunology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D000914:Antibodies, Viral