Our new work is out @NatureComms. We mapped differences in response to cytokines in naive and memory CD4 T cells. Wonderful collaboration with @TergetValidate and a great work led by @eddiecg and @BlagojeSoskic https://rdcu.be/b3y8u 

We combined proteomics, bulk RNAseq and scRNAseq to map early and late gene expression changes in naive (TN) and memory (TM) CD4 T cells to a range of cytokine conditions. While TN have been well studied in the context of cytokine stimulation, there is little information about TM

Naive and memory CD4 T cells switched on different programmes in response to the same cytokine stimulations, particularly when exposed to cytokines polarising towards Th2, Th17 and iTreg cell phenotypes.

Combining proteo-transcriptomic data we confirmed known and defined new cell markers for different cytokine induced cell states in both TN and TM.

Using scRNA-seq we show that transcriptionally, TN and TM cells form a continuum, rather than two distinct cell types. We refer to this as effectorness, as it is driven by increased expression of genes which determine T cell effector functions.

We show that the effectorness gradient is preserved upon stimulation and dictates how cells respond.

We modelled how effectorness modulates gene expression in response to cytokine: (i) by a cytokine irrespective of effectorness, (ii) as a function of effectorness irrespective of the cytokine; by effectorness and cytokine-stimulation acting (iii) independently or (iv) jointly

Of the 210 genes assoc with effectorness, 191 showed an interaction effect, including 12 that showed an effectorness dependency only in the presence of a given cytokine e.g. IL9 and Th17/iTreg cytokines.

Conclusion: CD4+ T cells form a transcriptional continuum characterized by an effectorness gradient which is determined by the expression of cytokine, chemokine, and granzyme genes and affects the response of cells to cytokine polarisation.