Antigen exposure reshapes chromatin architecture in central memory CD8+ T cells and imprints enhanced recall capacity [RNA-seq]
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ABSTRACT: Compared with naïve CD8+ T cells, antigen-experienced effector and central memory CD8 T cells show extensive CTCF redistribution and 3D genome reorgainzation, which underlie the transcriptomic diversification as well as recall capacity in response to secondary challenges.
Project description:Compared with naïve CD8+ T cells, antigen-experienced effector and central memory CD8 T cells show extensive CTCF redistribution and 3D genome reorgainzation, which underlie the transcriptomic diversification as well as recall capacity in response to secondary challenges.
Project description:Compared with naïve CD8+ T cells, antigen-experienced effector and central memory CD8 T cells show extensive CTCF redistribution and 3D genome reorgainzation, which underlie the transcriptomic diversification as well as recall capacity in response to secondary challenges.
Project description:The goal of this study is to determine the impact of Tcf1 deficiency on recall capacity of central memory CD8+ T (Tcm) cells. We demonstrate that loss of Tcf1 shows limited impact on Tcm cells at resting state, but severely comprimises activation of glycolysis and other key regulators during recall response. Based on these findings, we propose that Tcf1 preprograms the responsiveness of Tcm cells to secondary challenges.
Project description:Thymic stromal lymphopoietin (TSLP) is a cytokine that acts directly on CD4+ T cells and dendritic cells to promote progression of asthma, atopic dermatitis, and allergic inflammation. However, a direct role for TSLP in CD8+ T-cell primary responses remains controversial and its role in memory CD8+ T-cell responses to secondary viral infection is unknown. Here, we investigate the role of TSLP in both primary and recall responses using two different viral systems. Interestingly, TSLP limited the primary CD8+ T cell response to influenza but did not affect T cell function nor significantly alter the number of memory CD8+ T cells generated after influenza infection. However, TSLP inhibited memory CD8+ T cell responses to secondary viral infection with influenza or acute systemic LCMV infection. These data reveal a previously unappreciated role for TSLP on recall CD8+ T cell responses in response to viral infection, findings with potential translational implications.