Matches in SemOpenAlex for { <https://semopenalex.org/work/W2955338313> ?p ?o ?g. }
- W2955338313 abstract "SUMMARY CD4 memory T cells play an important role in protective immunity and are a key target in vaccine development. Many studies have focused on T central memory (TCM) cells, while the existence and functional significance of T follicular helper (TFH) memory cells is controversial. Here we show that TFH memory cells are highly susceptible to NAD induced cell death (NICD) during isolation from tissues, leading to their under-representation in prior studies. NICD blockade reveals the persistence of abundant TFH memory cells, with high expression of hallmark TFH markers, that persist to at least 400 days after infection, by which time TCM cells are no longer found. Using single cell RNA-seq we demonstrate that TFH memory cells are transcriptionally distinct from TCM cells, maintain stemness and self-renewal gene expression, and, in contrast to TCM cells, are multipotent following recall. Surprisingly, TFH memory cells concurrently express a distinct glycolytic signature similar to trained immune cells, including elevated expression of mTOR, HIF-1 and cAMP regulated genes. Late disruption of glycolysis/ICOS signaling leads to TFH memory cell depletion concomitant with decreased splenic plasma cells and circulating antibody titers, demonstrating both unique homeostatic regulation of memory TFH and their sustained function during the memory phase of the immune response. These results highlight the metabolic heterogeneity underlying distinct memory T cell subsets and establish TFH memory cells as an attractive target for the induction of long-lived adaptive immunity. HIGHLIGHTS Cell death during isolation from the tissue prevents the full recovery of TFH memory cells TFH memory cells are transcriptionally distinct from TCM cells and maintain a broader recall capacity TFH memory cells are maintained in the absence of antigen but require ICOS signaling and glycolysis TFH memory cells support late phase antibody production by splenic plasma cells" @default.
- W2955338313 created "2019-07-12" @default.
- W2955338313 creator A5009878373 @default.
- W2955338313 creator A5012990096 @default.
- W2955338313 creator A5017231006 @default.
- W2955338313 creator A5028007344 @default.
- W2955338313 creator A5031012128 @default.
- W2955338313 creator A5036672626 @default.
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- W2955338313 creator A5067042207 @default.
- W2955338313 creator A5071402164 @default.
- W2955338313 creator A5080001856 @default.
- W2955338313 creator A5080293719 @default.
- W2955338313 date "2019-06-23" @default.
- W2955338313 modified "2023-10-03" @default.
- W2955338313 title "Protection of bona fide T follicular memory cells during tissue isolation reveals their persistence, plasticity and functional impact" @default.
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