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Demers, Korey R; Makedonas, George; Buggert, Marcus; Eller, Michael A; Ratcliffe, Sarah J; Goonetilleke, Nilu; Li, Chris K; Eller, Leigh Anne; 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
PLOS pathogens, 08/2016, Letnik: 12, Številka: 8Journal Article
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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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