Using functional genomics to study human CD4+ T cells

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Date: Tuesday 12 May 2020
Time: 12:30-13:30
Speaker: Eddie Cano Gamez
Title: Using functional genomics to study human CD4+ T cells

Bio: Eddie is a PhD student at the Wellcome Sanger Institute and works with Gosia Trynka in the immune genomics group. He uses high-throughput ‘omics’ technologies to investigate the effect of cytokines in the function of human T cells and to understand the impact of genetic variation on T cell function.

Abstract: CD4+ T cells coordinate the immune response to pathogens. For instance, naive CD4+ T cells adapt their phenotype in response to cytokines, initiating different effector functions. However, the effect of cytokines on memory T cells remains largely understudied. This is due to the heterogeneity of the memory pool, which comprises multiple subpopulations. In this study, we performed single-cell RNA-sequencing of >40,000 human naive and memory CD4+ T cells polarised with five different cytokine combinations. We demonstrate that CD4+ T cells form a transcriptional continuum rather than discrete subpopulations. This continuum progresses from naive to central and effector memory cells, is associated with increased clonal expansion, and is accompanied by upregulation of chemokines and cytokines, thus constituting an effectorness gradient. We demonstrate that the response of CD4+ T cells to cytokines is shaped by this gradient and identify genes whose expression is controlled by cytokines in an effectorness-dependent manner. These results illustrate the heterogeneity of CD4+ T cells and begin to explain memory T cell plasticity.