Distinct Kinetics of Gag-Specific CD4+ and CD8+ T Cell Responses during Acute HIV-1 Infection

Abstract

HIV infection is characterized by a gradual deterioration of immune function, mainly in the CD4 compartment. To better understand the dynamics of HIV-specific T cells, we analyzed the kinetics and polyfunctional profiles of Gag-specific CD4+ and CD8+ T cell responses in 12 subtype C-infected individuals with different disease-progression profiles, ranging from acute to chronic HIV infection. The frequencies of Gag-responsive CD4+ and CD8+ T cells showed distinct temporal kinetics. The peak frequency of Gag-responsive IFN-γ+CD4+ T cells was observed at a median of 28 d (interquartile range: 21–81 d) post-Fiebig I/II staging, whereas Gag-specific IFN-γ+CD8+ T cell responses peaked at a median of 253 d (interquartile range: 136–401 d) and showed a significant biphasic expansion. The proportion of TNF-α–expressing cells within the IFN-γ+CD4+ T cell population increased (p = 0.001) over time, whereas TNF-α–expressing cells within IFN-γ+CD8+ T cells declined (p = 0.005). Both Gag-responsive CD4+ and CD8+ T cells showed decreased Ki67 expression within the first 120 d post-Fiebig I/II staging. Prior to the disappearance of Gag-responsive Ki67+CD4+ T cells, these cells positively correlated (p = 0.00038) with viremia, indicating that early Gag-responsive CD4 events are shaped by viral burden. No such associations were observed in the Gag-specific CD8+ T cell compartment. Overall, these observations indicated that circulating Gag-responsive CD4+ and CD8+ T cell frequencies and functions are not synchronous, and properties change rapidly at different tempos during early HIV infection.