P24.18
Background: Regulatory T cells (Tregs) suppress immune system activation and promote immunologic tolerance. Due to their impact on both innate and adaptive immune responses, Tregs have recently been explored as new targets for immunotherapy and vaccination strategies, as in cancer and transplantation settings. Moreover, Tregs garnered considerable interest in HIV pathogenesis, due to their potential impact in HIV-associated immune activation and viral replication. However, the role of Tregs in HIV infection remains incompletely understood. Here, we performed the first large scale transcriptome analysis of Tregs in HIV-infected individuals, which may provide important insight into Treg biology and support strategies for immune-based therapies and HIV-vaccine design.
Methods: We investigated the gene expression profiles of Tregs and conventional CD4+ T cells (Tconv) in HIV elite controllers (EC), individuals with chronic untreated HIV-1 infection (CU) and HIV-negative individuals. Following flow-based cell-sorting of Tregs and Tconv, whole genome expression analysis was performed using Illumina BeadChip technology. We screened for differential gene expression between the two T cell subsets and the study cohorts using the software R/bioconductor packages lumi and limma. Interesting candidate genes were further validated and investigated in ex vivo studies.
Results: We identified distinct group-specific variations in Treg signatures between EC and CU - with more than 40 genes significantly up/down-regulated. Those include several genes associated with interferon response (eg. IFI44) or transcriptional regulation (eg. PBX2), which are potentially relevant for the outcome of viral infections. Additionally, we observed HIV- and Treg-specific regulated genes in line with previously published studies, validating our experimental setup.
Conclusions: Our findings provide novel insight into the impact of Tregs on HIV pathogenesis. The results might be fundamental for novel concepts in HIV immunotherapy and vaccine design.
