Association of lymph-node antigens with lower Gag-specific central-memory and higher Env-specific effector-memory CD8+ T-cell frequencies in a macaque AIDS model

Abstract

Virus-specific CD8+ T cells exert strong suppressive pressure on human/simian immunodeficiency virus (HIV/SIV) replication. These responses have been intensively examined in peripheral blood mononuclear cells (PBMCs) but not fully analyzed in lymph nodes (LNs), where interaction between CD8[+] T cells and HIV/SIV-infected cells occurs. Here, we investigated target antigen specificity of CD8[+] T cells in LNs in a macaque AIDS model. Analysis of virus antigen-specific CD8[+] T-cell responses in the inguinal LNs obtained from twenty rhesus macaques in the chronic phase of SIV infection showed an inverse correlation between viral loads and frequencies of CD8[+] T cells with CD28[+]CD95[+] central memory phenotype targeting the N-terminal half of SIV core antigen (Gag-N). In contrast, analysis of LNs but not PBMCs revealed a positive correlation between viral loads and frequencies of CD8[+] T cells with CD28[−]CD95[+] effector memory phenotype targeting the N-terminal half of SIV envelope (Env-N), soluble antigen. Indeed, LNs with detectable SIV capsid p27 antigen in the germinal center exhibited significantly lower Gag-N-specific CD28[+] CD95[+] CD8[+] T-cell and higher Env-N-specific CD28[−]CD95[+] CD8[+] T-cell responses than those without detectable p27. These results imply that core and envelope antigen-specific CD8[+] T cells show different patterns of interactions with HIV/SIV-infected cells.