Cytotoxic Capacity of SIV-Specific CD8+ T Cells against Primary Autologous Targets Correlates with Immune Control in SIV-Infected Rhesus Macaques

Although the study of non-human primates has resulted in important advances for understanding hiv-specific immunity,a clear correlate of immune control over simian immunodeficiency virus (siv) replication has not been found to date. in this study,cd8+ t-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (rm) siv infection model as has been suggested in chronic hiv infection. sivmac251-infected human reverse transcriptase (htert)-transduced cd4+ t-cell clone targets were co-incubated with autologous macaque effector cells to measure infected cd4+ t-cell elimination (ice). twenty-three siv-infected rhesus macaques with widely varying plasma viral rna levels were evaluated in a blinded fashion. nineteen of 23 subjects (83%) were correctly classified as long-term nonprogressor/elite controller (ltnp/ec),slow progressor,progressor or siv-negative rhesus macaques based on measurements of ice (weighted kappa 0.75). ltnp/ec had higher median ice than progressors (67.3% [22.0-91.7%] vs. 23.7% [0.0-58.0%],p = 0.002). in addition,significant correlations between ice and viral load (r = -0.57,p = 0.01),and between granzyme b delivery and ice (r = 0.89,p<0.001) were observed. furthermore,the cd8+ t cells of ltnp/ec exhibited higher per-cell cytotoxic capacity than those of progressors (p = 0.004). these findings support that greater lytic granule loading of virus-specific cd8+ t cells and efficient delivery of active granzyme b to siv-infected targets are associated with superior control of siv infection in rhesus macaques,consistent with observations of hiv infection in humans. therefore,such measurements appear to represent a correlate of control of viral replication in chronic siv infection and their role as predictors of immunologic control in the vaccine setting should be evaluated.