Delayed differentiation of potent effector CD8 ⁺ T cells reducing viremia and reservoir seeding in acute HIV infection

Abstract

CD8+ T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The SIV model provided the proof of concept for a CD8+ T cell-mediated reservoir clearance but showed conflicting evidences on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8+ T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. Here we studied HIV-specific CD8+ T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8+ T cells generated as early as AHI stage 1 and 2 prior to peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8+ T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Importantly, their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8+ T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8+ T cells contribute to reducing the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design of interventions aiming at inducing these potent responses to cure HIV infection.

Very early antiretroviral therapy permits CD8 T cells to keep HIV reservoirs at bay

“…These participants received treatment during very early HIV infection and were grouped as stage 1, 2 and 3 with a median of 14, 16 and 19 days post-infection, respectively (18). They were able to show that the magnitude of HIV-specific CD8 T cells and their proliferative capacity were delayed on ART during stages 1 and 2 occurring before the peak of viremia.…”

Optimal maturation of the SIV-specific CD8+T-cell response after primary infection is associated with natural control of SIV. ANRS SIC study

“…To understand the mechanisms that contribute to immune control of SIV, we first monitored the proliferation and activation dynamics of total CD8 + T-cells in blood and lymphoid tissues from SICs and VIRs. Recent studies in cohorts of hyperacute HIV infected individuals indicate that the changes observed in the total CD8 + T-cell activation during acute infection may be largely related to changes in the HIV-specific CD8 + T-cell pool (Ndhlovu et al, 2015; Takata et al, 2017). The frequencies of CD8 + T-cells expressing Ki-67 in blood increased to maximum levels during primary infection (measured peak at day 15 p.i.…”

Effective Activation of Human Antigen-Presenting Cells and Cytotoxic CD8+ T Cells by a Calcium Phosphate-Based Nanoparticle Vaccine Delivery System

“…Lower concentrations of NPs or TLR ligands might also emphasize the advantage of CaP NPs. The induction of a potent CD8 + T cell response is very important for the control of viral infections, such as HIV or tumor disease [36]. In this regard, it has been demonstrated that triggering TLRs enhances the T cell priming process to increase the robustness of adaptive immune responses [37].…”