Association of Gag-Specific CD28+CD95+ CD8+ T-Cell Responses in Lymph Nodes With Lower Viral Loads

Background: Cumulative studies have suggested that HIV replication can be controlled by potent CD8+ T-cell responses. Individual viral proteins show different kinetics of expression and degradation, which affect efficacy of protein-derived epitope presentation to CD8+ T cells. Thus, some viral proteins can be the targets for effective CD8+ T cells more frequently. CD8+ T-cell responses have been examined in peripheral blood, but those in lymph nodes (LNs) have not been analyzed fully. Here, we investigated the relationship between viral loads and individual protein-specific CD8+ T-cell responses in LNs in a macaque AIDS model. Methodology: We used peripheral blood mononuclear cells (PBMCs) and lymphocytes in the inguinal LNs obtained in the chronic phase of SIVmac239 infection from 36 Burmese rhesus macaques. We examined viral protein-specific CD8+ T-cell responses in these PBMCs and LN-derived lymphocytes by detection of IFN-γ induction after stimulation with overlapping peptide pools and performed correlation analyses between these responses and viral loads. Results: Analyses using PBMCs revealed inverse correlation between viral loads and frequencies of CD8+ T cells, in particular central memory CD28+CD95+CD8+ T cells, specific for the N-terminal half of Gag (Gag-N). Analyses using LNs showed more significant inverse correlation between viral loads and Gag-N-specific CD28+CD95+CD8+ T-cell frequencies (Fig. 1). In contrast, frequencies of effector memory CD28-CD95+CD8+ T cells specific for the N-terminal half of Env (Env-N) in LNs as well as in PBMCs positively correlated with viral loads (Fig. 1). Percents of the CD28-CD95+ subset in Env-Nspecific CD8+ T cells were significantly higher than those in any other viral protein-specific CD8+ T cells. LNs without detectable SIV capsid p27 antigens had significantly higher frequencies of Gag-N-specific CD28+CD95+CD8+ T cells and lower frequencies of Env-N-specific CD28-CD95+CD8+ T cells than those with detectable p27. Conclusions: This study revealed the association of Gag-N-specific CD28+CD95+CD8+ T-cell frequencies in LNs with lower viral loads, supporting the notion that Gag-specific CD8+ T-cell responses can often contribute to HIV control. Interestingly, we further found positive correlation of Env-N-specific CD28-CD95+CD8+ T-cell frequencies with viral loads, implying that Env-N-specific CD8+ T-cell responses may not be effective against HIV/SIV replication.