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CD8 T cell differentiation has been associated with changes in the expression of long noncoding RNAs (lncRNAs). Yet, which and how lncRNAs regulate CD8 T cell responses following infection in vivo remains incompletely understood. We performed deep RNA-seq to map the lncRNA expression landscape of CD8 T cell subsets during infection and generated lncRNA knockout mouse models to evaluate the in vivo relevance of six lncRNAs. We identified to regulate effector CD8 T cell function and effector-to-memory differentiation. -deficient mice displayed increased CD44 Foxp3 regulatory T cells while the development of other immune cells, such as natural killer cells, was not affected. In CD8 T cells, deficiency resulted in a fine-tuned downregulation of transcription factors Id2 and T-bet and impaired KLRG1 and KLRG1 effector CD8 T cell proliferation and cytotoxicity as well as effector-to-memory CD8 T cell differentiation. The human orthologue of , , is also upstream of the transcriptional regulator and is highly expressed in human memory CD8 T cells. Taken together, represents a key regulatory layer that controls CD8 T cell differentiation.