Exhaustion of CD8+ T lymphocytes is a major barrier to effective clearance of chronic viral infection and cancer by the immune system. Transcriptional changes underlie the expansion and differentiation of a naive CD8+ T cell into various effector subsets, including the exhausted state. Experiments from other cell types have shown that the majority of the mammalian genome is transcribed, generating a large number of long, non-protein-coding RNAs (lncRNAs). These lncRNAs have been shown to play important roles in many cellular processes including histone modification, transcriptional regulation, and mRNA metabolism. To identify the role of lncRNAs in CD8+ T cell differentiation and exhaustion, we performed RNA-sequencing on functional and exhausted CD8+ T cells in both humans and mice. We identified over 1,000 expressed, previously un-annotated lncRNAs; of these, hundreds are differentially expressed over the course of CD8+ T cell differentiation. Exhausted CD8+ T cells express a unique set of lncRNAs, and this profile is altered with IL-2 treatment. These results suggest that lncRNAs play important roles in T cell differentiation and exhaustion, and further study is underway to determine their functional roles in anti-viral and anti-tumor immune responses.
Citation Format: William Hudson, Haydn Kissick, Masao Hashimoto, Rafi Ahmed. Long non-coding RNA expression during CD8+ T cell differentiation and exhaustion [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B142.
- ©2016 American Association for Cancer Research.