Stable individual immune response gene expression signatures in peripheral human CD4 cells foreshadow response to stimulation (HUM7P.324)

The complexity of molecular networks regulating the immune response presents challenges to measuring immune response potential in human populations. We measured gene expression in CD4+ peripheral blood cells from healthy subjects using RNAseq. RNA expression was assessed twice, one month apart to identify the subset of genes expressed stably within individuals over time yet discriminating individuals in a cohort. This immune response signature gene set then was used to identify and successfully order the immune response phenotypes of independent, unrelated subjects. Following a brief 4 hr stimulation of freshly isolated cells with anti-CD3/C28 antibody-coated beads, changes in gene expression were measured using a similar approach, defining individual response profiles and clustering response patterns. Examination of the RNA expression signatures of unstimulated CD4 cells revealed a gene subset which when analyzed for gene expression levels correctly aligned independent test subjects into the defined response-phenotype clusters following stimulation. Therefore, there exists a subset of genes stably expressed over time in circulating CD4+ cells which discriminate among individuals in a manner associated with immune response potential. Thus a systems approach can be used to describe the complex immune phenotypes of individuals in ways that might be useful in determining how individuals will respond to complex stimuli or in disease and treatment settings.