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

Korey R. Demers, George Makedonas, Marcus Buggert, Michael A. Eller, Sarah J. Ratcliffe, Nilu Goonetilleke, Chris K. Li, Leigh Anne Eller, Kathleen Rono, Lucas Maganga, Sorachai Nitayaphan, Hannah Kibuuka, Jean Pierre Routy, Mark K. Slifka, Barton F. Haynes, Andrew J. McMichael, Nicole F. Bernard, Merlin L. Robb, Michael R. Betts

    Research output: Contribution to journalArticle

    16 Scopus citations

    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.

    Original languageEnglish (US)
    Article numbere1005805
    JournalPLoS pathogens
    Volume12
    Issue number8
    DOIs
    StatePublished - Aug 2016

    ASJC Scopus subject areas

    • Parasitology
    • Microbiology
    • Immunology
    • Molecular Biology
    • Genetics
    • Virology

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    Demers, K. R., Makedonas, G., Buggert, M., Eller, M. A., Ratcliffe, S. J., Goonetilleke, N., Li, C. K., Eller, L. A., Rono, K., Maganga, L., Nitayaphan, S., Kibuuka, H., Routy, J. P., Slifka, M. K., Haynes, B. F., McMichael, A. J., Bernard, N. F., Robb, M. L., & Betts, M. R. (2016). Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection. PLoS pathogens, 12(8), [e1005805]. https://doi.org/10.1371/journal.ppat.1005805