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

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-bet(Lo) 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.