Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection

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  • Demers, Korey R.
    • Other Affiliation: Department of Microbiology; Perelman School of Medicine; University of Pennsylvania
  • Makedonas, George
    • Other Affiliation: Baylor College of Medicine; Department of Pediatrics Texas Children’s Hospital; Feigin Center
  • Buggert, Marcus
    • Other Affiliation: Center for Infectious Medicine; Department of Medicine; Karolinska Institute; Karolinksa University Hospital Huddinge
  • Eller, Michael A.
    • Other Affiliation: U.S. Military HIV Research Program; Walter Reed Army Institute of Research
  • Ratcliffe, Sarah J.
    • Other Affiliation: Department of Biostatistics and Epidemiology; Perelman School of Medicine; University of Pennsylvania
  • Goonetilleke, Nilu
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
    • Other Affiliation: Medical Research Council Human Immunology Unit; Weatherall Institute of Molecular Medicine; University of Oxford
  • Li, Chris K.
    • Other Affiliation: Medical Research Council Human Immunology Unit; Weatherall Institute of Molecular Medicine; University of Oxford
  • Eller, Leigh Anne
    • Other Affiliation: U.S. Military HIV Research Program; Walter Reed Army Institute of Research
  • Rono, Kathleen
    • Other Affiliation: Walter Reed Project-Kenya Medical Research Institute
  • Maganga, Lucas
    • Other Affiliation: Mbeya Medical Research Centre
  • Nitayaphan, Sorachai
    • Other Affiliation: Department of Retrovirology; United States Army Medical Component; Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS)
  • Kibuuka, Hannah
    • Other Affiliation: Makerere University Walter Reed Project; Makerere University Medical School
  • Routy, Jean-Pierre
    • Other Affiliation: Division of Hematology & Chronic Viral Illness Service; McGill University Health Centre
  • Slifka, Mark K.
    • Other Affiliation: Division of Neuroscience; Oregon National Primate Research Center; Oregon Health and Science University
  • Haynes, Barton F.
    • Other Affiliation: Duke Human Vaccine Institute; Duke University
  • McMichael, Andrew J.
    • ORCID: 0000-0002-9101-7478
    • Other Affiliation: NDM Research Building; University of Oxford
  • Bernard, Nicole F.
    • Other Affiliation: Research Institute of the McGill University Health Centre,
  • Robb, Merlin L.
    • Other Affiliation: U.S. Military HIV Research Program; Walter Reed Army Institute of Research
  • Betts, Michael R.
    • Other Affiliation: Department of Microbiology; Perelman School of Medicine; University of Pennsylvania
Abstract
  • The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection.
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • PLoS Pathogens
Journal volume
  • 12
Journal issue
  • 8
Page start
  • e1005805
Language
  • English
ISSN
  • 1553-7374
  • 1553-7366

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