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.