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

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Date
2016Author
Demers, Korey R.
Makedonas, George
Buggert, Marcus
Eller, Michael A.
Ratcliffe, Sarah J.
Goonetilleke, Nilu
Li, Chris K.
Anne Eller, Leigh
Rono, Kathleen
Maganga, Lucas
Nitayaphan, Sorachai
Kibuuka, Hannah
Routy, Jean-Pierre
Slifka, Mark K.
Haynes, Barton F.
McMichael, Andrew J.
Bernard, Nicole F.
Robb, Merlin L.
Betts, Michael R.
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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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