Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection
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Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS Pathogens
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.
Description
Keywords
Temporal Dynamics, CD8+ T Cell, Primary HIV Infection
Citation
Demers KR, Makedonas G, Buggert M, Eller MA, Ratcliffe SJ, Goonetilleke N, et al. (2016) Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection. PLoS Pathog 12(8): e1005805. doi:10.1371/journal. ppat.1005805