Distinct kinetics of Gag-specific CD4+ and CD8+ T cell responses during acute HIV-1 infection

C Riou, VV Ganusov, S Campion… - The Journal of …, 2012 - journals.aai.org
C Riou, VV Ganusov, S Campion, M Mlotshwa, MKP Liu, VE Whale, N Goonetilleke
The Journal of Immunology, 2012journals.aai.org
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 …
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.
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