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.
Highlights
Virus-specific CD8+ T cells exert strong suppressive pressure on human/simian immunodeficiency virus (HIV/SIV) replication
CD8+ T-cell responses in the inguinal lymph nodes (LNs) and peripheral blood mononuclear cells (PBMCs) obtained from twenty rhesus macaques in the chronic phase of SIV infection (Fig. 1)
An inverse correlation between plasma viral loads and Gag-specific CD8+ T-cell responses in PBMCs was previously shown by a large cohort of human immunodeficiency virus (HIV)-1-infected individuals[22,23,24]
Summary
Virus-specific CD8+ T cells exert strong suppressive pressure on human/simian immunodeficiency virus (HIV/SIV) replication. 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). Studies in macaque AIDS models have indicated simian immunodeficiency virus (SIV) control by Gag antigen-specific CD8+ T-cell responses[12,20,21] In addition to these studies on HIV/SIV controllers, analysis in a large cohort of HIV-infected individuals showed that Gag-specific CD8+ T-cell responses are associated with lower viral loads[22,23,24]. Our analysis indicated that viral loads were correlated inversely with SIV core Gag antigen-specific central-memory but positively with SIV envelope (Env) antigen-specific effector-memory CD8+ T-cell frequencies in LNs
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