Demers, Korey R.Makedonas, GeorgeBuggert, MarcusEller, Michael A.Ratcliffe, Sarah J.Goonetilleke, NiluLi, Chris K.Anne Eller, LeighRono, KathleenMaganga, LucasNitayaphan, SorachaiKibuuka, HannahRouty, Jean-PierreSlifka, Mark K.Haynes, Barton F.McMichael, Andrew J.Bernard, Nicole F.Robb, Merlin L.Betts, Michael R.2022-12-152022-12-152016Demers 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.100580510.1371/journal. ppat.1005805https://nru.uncst.go.ug/handle/123456789/6340The 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.enTemporal DynamicsCD8+ T CellPrimary HIV InfectionArticle