tetano
Editor, Senior Moderator
Cell Rep
. 2021 May 25;35(8):109174.
doi: 10.1016/j.celrep.2021.109174.
Divergent clonal differentiation trajectories establish CD8 [SUP]+[/SUP] memory T cell heterogeneity during acute viral infections in humans
Jeff E Mold[SUP] 1 [/SUP], Laurent Modolo[SUP] 2 [/SUP], Joanna Hård[SUP] 1 [/SUP], Margherita Zamboni[SUP] 1 [/SUP], Anton J M Larsson[SUP] 1 [/SUP], Moa Stenudd[SUP] 1 [/SUP], Carl-Johan Eriksson[SUP] 1 [/SUP], Ghislain Durif[SUP] 2 [/SUP], Patrik L Ståhl[SUP] 3 [/SUP], Erik Borgström[SUP] 4 [/SUP], Simone Picelli[SUP] 1 [/SUP], Björn Reinius[SUP] 5 [/SUP], Rickard Sandberg[SUP] 1 [/SUP], Pedro Réu[SUP] 1 [/SUP], Carlos Talavera-Lopez[SUP] 1 [/SUP], Björn Andersson[SUP] 1 [/SUP], Kim Blom[SUP] 6 [/SUP], Johan K Sandberg[SUP] 6 [/SUP], Franck Picard[SUP] 2 [/SUP], Jakob Michaëlsson[SUP] 7 [/SUP], Jonas Frisén[SUP] 8 [/SUP]
Affiliations
Abstract
The CD8[SUP]+[/SUP] T cell response to an antigen is composed of many T cell clones with unique T cell receptors, together forming a heterogeneous repertoire of effector and memory cells. How individual T cell clones contribute to this heterogeneity throughout immune responses remains largely unknown. In this study, we longitudinally track human CD8[SUP]+[/SUP] T cell clones expanding in response to yellow fever virus (YFV) vaccination at the single-cell level. We observed a drop in clonal diversity in blood from the acute to memory phase, suggesting that clonal selection shapes the circulating memory repertoire. Clones in the memory phase display biased differentiation trajectories along a gradient from stem cell to terminally differentiated effector memory fates. In secondary responses, YFV- and influenza-specific CD8[SUP]+[/SUP] T cell clones are poised to recapitulate skewed differentiation trajectories. Collectively, we show that the sum of distinct clonal phenotypes results in the multifaceted human T cell response to acute viral infections.
Keywords: memory CD8(+) T cells, yellow fever virus, single-cell RNA sequencing.
. 2021 May 25;35(8):109174.
doi: 10.1016/j.celrep.2021.109174.
Divergent clonal differentiation trajectories establish CD8 [SUP]+[/SUP] memory T cell heterogeneity during acute viral infections in humans
Jeff E Mold[SUP] 1 [/SUP], Laurent Modolo[SUP] 2 [/SUP], Joanna Hård[SUP] 1 [/SUP], Margherita Zamboni[SUP] 1 [/SUP], Anton J M Larsson[SUP] 1 [/SUP], Moa Stenudd[SUP] 1 [/SUP], Carl-Johan Eriksson[SUP] 1 [/SUP], Ghislain Durif[SUP] 2 [/SUP], Patrik L Ståhl[SUP] 3 [/SUP], Erik Borgström[SUP] 4 [/SUP], Simone Picelli[SUP] 1 [/SUP], Björn Reinius[SUP] 5 [/SUP], Rickard Sandberg[SUP] 1 [/SUP], Pedro Réu[SUP] 1 [/SUP], Carlos Talavera-Lopez[SUP] 1 [/SUP], Björn Andersson[SUP] 1 [/SUP], Kim Blom[SUP] 6 [/SUP], Johan K Sandberg[SUP] 6 [/SUP], Franck Picard[SUP] 2 [/SUP], Jakob Michaëlsson[SUP] 7 [/SUP], Jonas Frisén[SUP] 8 [/SUP]
Affiliations
- PMID: 34038736
- DOI: 10.1016/j.celrep.2021.109174
Abstract
The CD8[SUP]+[/SUP] T cell response to an antigen is composed of many T cell clones with unique T cell receptors, together forming a heterogeneous repertoire of effector and memory cells. How individual T cell clones contribute to this heterogeneity throughout immune responses remains largely unknown. In this study, we longitudinally track human CD8[SUP]+[/SUP] T cell clones expanding in response to yellow fever virus (YFV) vaccination at the single-cell level. We observed a drop in clonal diversity in blood from the acute to memory phase, suggesting that clonal selection shapes the circulating memory repertoire. Clones in the memory phase display biased differentiation trajectories along a gradient from stem cell to terminally differentiated effector memory fates. In secondary responses, YFV- and influenza-specific CD8[SUP]+[/SUP] T cell clones are poised to recapitulate skewed differentiation trajectories. Collectively, we show that the sum of distinct clonal phenotypes results in the multifaceted human T cell response to acute viral infections.
Keywords: memory CD8(+) T cells, yellow fever virus, single-cell RNA sequencing.