Late-phase dominance of a single epitope-specific CD8+ T-cell response in passive neutralizing antibody-infused simian immunodeficiency virus controllers

Abstract

Objective: Analysis of the quantity and quality of epitope-specific CD8 þ T-cell responses is crucial for understanding the mechanism of HIV/simian immunodeficiency virus (SIV) replication control. We have previously shown that acute-phase passive infusion of neutralizing antibodies (NAbs) results in augmented broad T-cell responses and robust SIV mac239 control in rhesus macaques. Analyzing long-term dynamics of CD8 þ T-cell responses in these SIV controllers provides important insights into designing lasting anti-HIV immunity.Design: We analyzed dynamics and metabolic/functional profiles of SIV-specific CD8 þ T-cell responses in rhesus macaques that controlled SIV mac239 replication following acute-phase passive NAb infusion.Methods: SIV epitope-specific CD8 þ T-cell responses in peripheral blood at multiple chronic-phase time points were investigated in four passive NAb-infused SIV controllers. In particular, expression patterns of Eomesodermin (Eomes), phosphorylated AMP kinase (pAMPK), CD28 and programmed death-1 (PD-1) were examined.Results: In the NAb-infused SIV controllers, a single epitope-specific CD8 þ T-cell response detected from acute infection and maintaining low levels up to year 1 showed a surge thereafter, up to year 2 postchallenge. Retention of an effector-skewed and unexhausted Eomes-high/pAMPK-low/CD28-negative/PD-1-low subpopulation in these epitope-specific CD8 þ T cells implicated their front-line commitment in residual viral replication control. Conclusion:In long-term SIV control following acute-phase passive NAb infusion, a single-epitope, high-quality CTL response was dominantly induced in the chronic phase. These results likely describe one favorable pattern of immunodominant epitope-specific CD8 þ T-cell preservation and suggest the importance of incorporating metabolic marker signatures for understanding NAb/T-cell synergism-based HIV/SIV control .

Association of envelope-specific B-cell differentiation and viral selective pressure signatures in HIV-1 CRF01_AE infection

“…For example, passive NAb transfer is highlighted for impacting viremia in HIV-1-infected individuals [58] and simian-HIV (SHIV)-infected macaques [59][60][61]. Paralleling these, acute-phase simian immunodeficiency virus (SIV)-specific NAb infusion evokes functional CD4 þ /CD8 þ T-cell augmentation, attaining lasting SIV control [62,63]. Current analyses on B-cell responses may also potentially contribute to designing new strategies for harnessing HIV-specific B cells evoking such mechanisms.…”