Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques

To determine the role of CD8+ T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8+ T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.

• Publication year

  1999

• Venue

  Journal of Experimental Medicine

• Publication date

  1999-03-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.189.6.991PMID 10075982PMCID 2193038
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Administration of an Anti-CD8 Monoclonal Antibody Interferes with the Clearance of Chimeric Simian/Human Immunodeficiency Virus during Primary Infections of Rhesus Macaques

  1998cited by this paper
• Spectral Genotyping of Human Alleles

  1998cited by this paper
• Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA.

  1998cited by this paper
• Temporal Analyses of Virus Replication, Immune Responses, and Efficacy in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine

  1998cited by this paper
• Inhibition of Simian Immunodeficiency Virus (SIV) Replication by CD8+ T Lymphocytes from Macaques Immunized with Live Attenuated SIV

  1998cited by this paper
• Spectral genotyping of human alleles.

  1998cited by this paper
• Plasma SIV RNA Viral Load Determination by Real-Time Quantification of Product Generation in Reverse Transcriptase-Polymerase Chain Reaction

  1998cited by this paper
• Mechanisms of Protection Induced by Attenuated Simian Immunodeficiency Virus II. Lymphocyte Depletion Does Not Abrogate Protection

  1998cited by this paper
• Influence of delayed viral production on viral dynamics in HIV-1 infected patients.

  1998influential reference
• Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus

  1997influential reference
• Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa.

  1997cited by this paper
• Epstein-Barr virus-specific cytotoxic T cell responses in HIV-1 infection: different kinetics in patients progressing to opportunistic infection or non-Hodgkin's lymphoma.

  1997cited by this paper
• Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia.

  1997cited by this paper
• Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms

  1997cited by this paper
• Virus dynamics and drug therapy.

  1997cited by this paper
• Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes (CTL), virus load, and CD4 T cell loss: evidence supporting a protective role for CTL in vivo.

  1997cited by this paper
• Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serum.

  1997cited by this paper
• Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma

  1996cited by this paper
• Direct Observation of Vortex Dynamics in Superconducting Films with Regular Arrays of Defects

  1996cited by this paper
• Molecular Beacons: Probes that Fluoresce upon Hybridization

  1996cited by this paper
• HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time

  1996cited by this paper
• Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics

  1995cited by this paper
• Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques

  1995cited by this paper
• HIV‐2-specific cytotoxic T‐lymphocyte activity is inversely related to proviral load

  1995cited by this paper
• High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors

  1995cited by this paper
• Errata

  1995cited by this paper
• Formation of simian immunodeficiency virus long terminal repeat circles in resting T cells requires both T cell receptor- and IL-2-dependent activation

  1995cited by this paper
• Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.

  1995cited by this paper
• Cellular immune response of rhesus monkeys infected with a partially attenuated nef deletion mutant of the simian immunodeficiency virus.

  1995cited by this paper
• CD8+ T cells suppress human immunodeficiency virus replication by inhibiting viral transcription.

  1995cited by this paper
• Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells

  1995cited by this paper
• HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women

  1995cited by this paper
• Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome

  1994cited by this paper
• Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection

  1994cited by this paper
• Quantitative analysis of the human immunodeficiency virus type 1 (HIV- 1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein- Barr virus in late disease

  1993cited by this paper
• Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene.

  1992cited by this paper
• Cytokine release and dynamics of leukocyte populations after CD3/TCR monoclonal antibody treatment

  1992cited by this paper
• Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses

  1988cited by this paper
• Human cytomegalovirus‐specific cytotoxic T cells: their precursor frequency and stage specificity

  1988cited by this paper
• Experimental allergic encephalomyelitis in rhesus monkeys: II. Treatment of EAE with anti-T lymphocyte subset monoclonal antibodies.

  1987cited by this paper
• CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication.

  1986cited by this paper
• THE INFLUENCE OF OKT8F TREATMENT ON ALLOGRAFT SURVIVAL IN RHESUS MONKEYS

  1986cited by this paper
• Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.

  1984cited by this paper
• Cytotoxic T-cell immunity to influenza.

  1983cited by this paper
• Long-term T-cell-mediated immunity to Epstein-Barr virus.

  1981cited by this paper
• Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus

  1978cited by this paper
• Dramatic Rise in Plasma Viremia after Cd8 Ϩ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques

  year unknowncited by this paper

• Recapitulating the qualities of HIV-specific CD8+ T cells from spontaneous controllers.

  2026cites this paper
• Duration of Initial Viremia Modulates Functional Properties of HIV-specific T Cell Receptors

  2026cites this paper
• Understanding the performance of HIV-1 viral vector vaccines: adenovirus and poxvirus case studies

  2026cites this paper
• Molecular Mechanisms Governing CD8 T Cell Differentiation and Checkpoint Inhibitor Response in Cancer.

  2025cites this paper
• The pathogenicity and multi-organ proteomic profiles of Mpox virus infection in SIVmac239-infected rhesus macaques

  2025cites this paper
• IL-27 effects on HIVGag-specific CD4 and CD8 T cell function.

  2025cites this paper
• Therapeutic CD8+ T cell tissue retention and immunomodulation during ART interruption fail to prevent SIV rebound

  2025cites this paper
• HDAC1 controls the generation and maintenance of effector-like CD8+ T cells during chronic viral infection

  2025cites this paper
• Epigenetic regulation of T cell exhaustion in cancer

  2025cites this paper
• Continuous expression of TOX safeguards exhausted CD8 T cell epigenetic fate.

  2025cites this paper
• Early treatment and PD1 inhibition enhance HIV-specific functionality of follicular CD8+ T cells

  2025cites this paper
• Deciphering T-cell exhaustion in the tumor microenvironment: paving the way for innovative solid tumor therapies

  2025cites this paper
• Energy demanding RNA and protein metabolism drive dysfunctionality of HIV-specific T cell changes during chronic HIV infection

  2024cites this paper
• Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection

  2024influential citation
• PD-1 knockout on cytotoxic primary murine CD8+ T cells improves their motility in retrovirus infected mice

  2024cites this paper
• Harnessing innate immune pathways for therapeutic advancement in cancer

  2024cites this paper
• Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection

  2024cites this paper
• Altering β Cell Antigen Exposure to Exhausted CD8+ T Cells Prevents Autoimmune Diabetes in Mice.

  2024cites this paper
• Innate protection against intrarectal SIV acquisition by a live SHIV vaccine

  2024cites this paper
• Durable lymphocyte subset elimination upon a single dose of AAV-delivered depletion antibody dissects immune control of chronic viral infection.

  2024cites this paper
• Tissue-Specific DNA Methylation Changes in CD8+ T Cells During Chronic Simian Immunodeficiency Virus Infection of Infant Rhesus Macaques

  2024cites this paper
• T Cell Exhaustion.

  2024cites this paper
• Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates

  2024cites this paper
• Generating and measuring effective vaccine-elicited HIV-specific CD8+ T cell responses

  2023cites this paper
• CD8+ Lymphocytes from Healthy Blood Donors Secrete Antiviral Levels of Interferon-Alpha

  2023influential citation
• New developments in treatment of HIV

  2023cites this paper
• T‐cell heterogeneity, progenitor–progeny relationships, and function during latent and chronic viral infections

  2023cites this paper
• Immunological mechanisms of tolerance: Central, peripheral and the role of T and B cells

  2023cites this paper
• Hierarchical transcriptional network governing heterogeneous T cell exhaustion and its implications for immune checkpoint blockade

  2023cites this paper
• Recent advances in CD8+ T cell-based immune therapies for HIV cure

  2023cites this paper
• Detecting and Resetting Tipping Points to Create More HIV Post-Treatment Controllers with Bifurcation and Sensitivity Analysis

  2023cites this paper
• Viral Persistence in the Gut-Associated Lymphoid Tissue and Barriers to HIV Cure

  2023cites this paper
• The latency-reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific T cells

  2023cites this paper
• Mathematical modeling indicates that regulatory inhibition of CD8+ T cell cytotoxicity can limit efficacy of IL-15 immunotherapy in cases of high pre-treatment SIV viral load

  2023cites this paper
• Regulatory T cells suppress the motility of cytotoxic T cells in Friend retrovirus–infected mice

  2023cites this paper
• Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251

  2023cites this paper
• Exhausted CD8+ T cells face a developmental fork in the road.

  2023cites this paper
• CD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production

  2023cites this paper
• CD8+ T cells in the cancer-immunity cycle.

  2023cites this paper
• Nano-vaccines for gene delivery against HIV-1 infection

  2023cites this paper
• Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+ T cell response during acute and chronic toxoplasmosis

  2022cites this paper
• The Rational Combination Strategy of Immunomodulatory Latency Reversing Agents and Novel Immunotherapy to Achieve HIV-1 Cure

  2022cites this paper
• Enhanced Cross-Reactive and Polyfunctional Effector-Memory T Cell Responses by ICVAX—a Human PD1-Based Bivalent HIV-1 Gag-p41 Mosaic DNA Vaccine

  2022cites this paper
• Progress Towards a Therapeutic HIV DNA Vaccine

  2022cites this paper
• Enhanced STAT5a activation rewires exhausted CD8 T cells during chronic stimulation to acquire a hybrid durable effector like state

  2022cites this paper
• HIV specific CD8+ TRM-like cells in tonsils express exhaustive signatures in the absence of natural HIV control

  2022cites this paper
• Non-cytotoxic functions of CD8 T cells: “repentance of a serial killer”

  2022influential citation
• Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy

  2022cites this paper
• TLR4 signaling in presence of HIV-induced activation enhances programmed death ligand-1 expression on human plasmacytoid dendritic cells and modulates their function

  2022cites this paper
• Clonal lineage tracing reveals mechanisms skewing CD8+ T cell fate decisions in chronic infection

  2022cites this paper
• Interleukin-21 in Viral Infections

  2021cites this paper
• Preventive HIV Vaccines-Leveraging on Lessons from the Past to Pave the Way Forward

  2021cites this paper
• IL-27 induces IFN/STAT1-dependent genes and enhances function of TIGIT+ HIVGag-specific T cells

  2021cites this paper
• Compartmentalized T cell profile in the lungs of patients with HIV-1-associated pulmonary Kaposi sarcoma

  2021cites this paper
• Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity

  2021cites this paper
• HLA-E-restricted HIV-1-specific CD8+ T cell responses in natural infection.

  2021cites this paper
• Elevated HIV Infection of CD4 T Cells in MRKAd5 Vaccine Recipients Due to CD8 T Cells Targeting Adapted Epitopes

  2021cites this paper
• Microbial mismanagement: how inadequate treatments for vaginal dysbiosis drive the HIV epidemic in women

  2021cites this paper
• CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment.

  2021cites this paper
• Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination

  2021cites this paper
• The CD8+ T Cell Noncytotoxic Antiviral Responses

  2021cites this paper
• Heterologous arenavirus vector prime-boost overrules self-tolerance for efficient tumor-specific CD8 T cell attack

  2021cites this paper
• Potential Utility of Natural Killer Cells for Eliminating Cells Harboring Reactivated Latent HIV-1 Following the Removal of CD8+ T Cell-Mediated Pro-Latency Effect(s)

  2021cites this paper
• [In vivo protective mechanisms of neutralizing antibodies against simian immunodeficiency virus replicatio].

  2021cites this paper
• CD8+ T cell differentiation and dysfunction in cancer

  2021cites this paper
• The Role of Immunomodulatory Receptors in the Pathogenesis of HIV Infection: A Therapeutic Opportunity for HIV Cure?

  2020cites this paper
• Immune outcomes of Zika virus infection in nonhuman primates

  2020cites this paper
• Jigsaw falling into place: A review and perspective of lymphoid tissue CD8+ T cells and control of HIV

  2020cites this paper
• Custommune: a web tool to design personalized and population-targeted vaccine epitopes

  2020cites this paper
• Innate and Adaptive Anti-SIV Responses in Macaque Semen: Implications for Infectivity and Risk of Transmission

  2020cites this paper
• Mathematical models for HIV treatment : A schematic review

  2020cites this paper
• MAVS Genetic Variation Is Associated with Decreased HIV-1 Replication In Vitro and Reduced CD4+ T Cell Infection in HIV-1-Infected Individuals

  2020cites this paper
• CD8+ T cells in HIV control, cure and prevention

  2020cites this paper
• Induction of Transient Virus Replication Facilitates Antigen-Independent Isolation of SIV-Specific Monoclonal Antibodies

  2020cites this paper
• The immunologic dominance of an epitope within a rationally designed poly-epitope vaccine is influenced by multiple factors.

  2020cites this paper
• Clinical Study Protocol

  2020cites this paper
• CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+T cells favors viral control in chronic HBV infection.

  2020cites this paper
• Epigenetic and Signaling Pathways Regulating the Maintenance of CD8 T Cell Identity and Function

  2020cites this paper
• A key control point in the T cell response to chronic infection and neoplasia: FOXO1.

  2020cites this paper
• The role of CD8 T cells in controlling HIV beyond the antigen‐specific face

  2020cites this paper
• Mathematical modeling of N-803 treatment in SIV-infected non-human primates

  2020cites this paper
• Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion

  2020cites this paper
• Origin and fine-tuning of effector CD8 T cell subpopulations in chronic infection.

  2020cites this paper
• Exhausted T cells and epigenetic status

  2020cites this paper
• Simian Immunodeficiency Virus-Infected Memory CD4+ T Cells Infiltrate to the Site of Infected Macrophages in the Neuroparenchyma of a Chronic Macaque Model of Neurological Complications of AIDS

  2020cites this paper
• Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription

  2020cites this paper
• CD8β Depletion Does Not Prevent Control of Viral Replication or Protection from Challenge in Macaques Chronically Infected with a Live Attenuated Simian Immunodeficiency Virus

  2019cites this paper
• Extensive CD8β depletion does not prevent control of viral replication or protection from challenge in macaques chronically infected with a live attenuated simian immunodeficiency virus

  2019cites this paper
• PD-1 Dynamically Regulates Inflammation and Development of Brain-Resident Memory CD8 T Cells During Persistent Viral Encephalitis

  2019cites this paper
• Transgene IL-21-Engineered T Cell-Based Vaccine Potently Converts CTL Exhaustion via the Activation of the mTORC1 Pathway in Chronic Infection

  2019cites this paper
• Heterogeneity and fate choice: T cell exhaustion in cancer and chronic infections.

  2019cites this paper
• CD8+ lymphocytes modulate Zika virus dynamics and tissue 1 dissemination and orchestrate antiviral immunity 2

  2019cites this paper
• Low levels of SIV-specific CD8+ T cells in germinal centers characterizes acute SIV infection

  2019cites this paper
• Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill

  2019cites this paper
• T‐cell exhaustion in HIV infection

  2019cites this paper
• CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer.

  2019cites this paper
• CD8+ T cell-based strong selective pressure on multiple simian immunodeficiency virus targets in macaques possessing a protective MHC class I haplotype.

  2019cites this paper
• Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus

  2019cites this paper
• Cervicovaginal inflammatory cytokine and chemokine responses to two different SIV vaccines in female mauritian cynomolgus macaques

  2019cites this paper
• Does B Cell Follicle Exclusion of CD8+ T Cells Make Lymph Nodes Sanctuaries of HIV Replication?

  2019cites this paper