Developmentally distinct CD4⁺T_reglineages shape the CD8⁺T cell response to acuteListeriainfection

Abstract

Significance The CD4 + T reg response following acute Listeria infection is heterogeneous and deploys two distinct modes of suppression coinciding with initial pathogen exposure and resolution of infection. This bimodal suppression of CD8 + T cells during priming and contraction is mediated by separate T reg lineages. These findings make a significant contribution to our understanding of the functional plasticity inherent within T reg s , which allows these cells to serve as a sensitive and dynamic cellular rheostat for the immune system to prevent autoimmune pathology in the face of inflammation attendant to acute infection, enable expansion of the pathogen-specific response needed to control the infection, and reestablish immune homeostasis after the threat has been contained.

Tregs tango with killer cells in acute infection

“…In PNAS, Dolina et al. ( 8 ) demonstrate that distinct Treg cell populations arise during acute Listeria monocytogenes ( Lm ) infection, with discrete effects at regulating CD8 + T cell responses during the priming versus contraction phases ( Fig. 1 ).…”

“…To investigate the role of Treg cells in regulating the adaptive immune response against acute infection, Dolina et al. ( 8 ) infected C57BL/6 mice with Lm Δ actA -Ova (an attenuated Listeria strain with deletion of the virulence factor actA and expression of chicken ovalbumin [Ova]), which could induce distinct Treg responses according to low or high dose of bacterial challenge ( 10 ). They found that there were two distinct waves of Treg cell responses that occurred at days 1 and 7 after Listeria infection (called day 1 and day 7 Treg cells, respectively).…”

“…Dolina et al. ( 8 ) next performed lineage tracing assay by labeling day 1 and 7 Treg cells from Foxp3-eGFP reporter mice with EdU (5-ethynyl-2′-deoxyuridine) and BrdU (bromodeoxyuridine), respectively. They found that most labeled populations were either single positive for EdU or BrdU, suggesting that day 1 and day 7 Treg cells may not follow the same differentiation trajectory.…”

“…Dolina et al. ( 8 ) also performed hemisplenectomy to isolate Treg cells from the same host at these two time points and then compared the T cell receptor repertoires of day 1 and day 7 Treg cells. The authors found that these two Treg subpopulations were clonally distinct.…”

“…Based on these results, Dolina et al. ( 8 ) next explored the underlying mechanisms by RNA sequencing (RNA-seq). Using unbiased hierarchical clustering, they found that Treg cell signature genes were grouped into three gene clusters, with differential expression patterns in days 0, 1, and 7 Treg cells.…”