Longitudinal human CD8+ T-cell fate following yellow fever vaccination 3548

Abstract Description CD8+ T-cells are critical effectors in the immune response against viral infections and cancers. A long-standing question within T-cell immunology concerns the mechanisms that govern which cells give rise to long lived memory CD8+ T-cells. We have profiled Yellow Fever Virus (YFV) specific CD8+ T-cells from blood from four different donors at four different timepoints spanning up to + 3 years post YFV-vaccination and performed Smartseq3 single cell RNA sequencing on over 30k cells. Using this dataset, we have longitudinally profiled thousands of unique clonal T cell populations as they differentiate from early effectors (GZMB+Ki67+) to long-lived stem (TCF7+CCR7+) and effector memory (ZEB2+GZMB+) subsets. We provide evidence of clonal bias towards stem or effector memory phenotypes in the late memory phase of the response. Most long-lived memory cells, regardless of memory differentiation state, exhibit evidence of expanded, rapidly dividing effector cells during the acute phase of the response. We use full-length transcript sequencing to identify mitochondrial mutations as subclonal markers for labeling branchpoints within clones, that may reveal steps leading to the establishment of long-lived memory T cells following the resolution of the acute phase of the vaccine response. We hope to build on our findings to begin to understand the complex processes that lead to long-lived memory T cell development and diversification during successful adaptive immune responses. Funding Sources Swedish Research Council, the Swedish Cancer Society, the Karolinska Institute, the Strategic Research Programme in Stem Cells and Regenerative Medicine at Karolinska Institutet (StratRegen), the Swedish Society for Strategic Research, and Knut och Alice Wallenbergs Stiftelse. Topic Categories Viral Immunology (VIR)