Metabolic pathway activation distinguishes transcriptional signatures of CD8+ T cells from HIV-1 elite controllers

OBJECTIVE:Elite controllers, defined as persons maintaining undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, represent living evidence that sustained, natural control of HIV-1 is possible, at least in relatively rare instances. Understanding the complex immunologic and virologic characteristics of these specific patients holds promise for inducing drug-free control of HIV-1 in broader populations of HIV-1 infected patients. DESIGN:We used an unbiased transcriptional profiling approach to characterize CD8 T cells, the strongest correlate of HIV-1 immune control identified thus far, in a large cohort of elite controllers (n = 51); highly active antiretrovial therapy (HAART)-treated patients (n = 32) and HIV-1 negative (n = 10) served as reference cohorts. METHODS:We isolated mRNA from total CD8 T cells isolated from peripheral blood mononuclear cell (PBMC) of each individual followed by microarray analysis of the transcriptional signatures. RESULTS:We observed profound transcriptional differences [590 transcripts, false discovery rate (FDR)-adjusted P