Durable CD4 T-Cell Memory Generation Depends on Persistence of High Levels of Infection at an Effector Checkpoint that Determines Multiple Fates.
Journal
Cold Spring Harbor perspectives in biology
ISSN: 1943-0264
Titre abrégé: Cold Spring Harb Perspect Biol
Pays: United States
ID NLM: 101513680
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
pubmed:
28
4
2021
medline:
24
2
2022
entrez:
27
4
2021
Statut:
epublish
Résumé
We have discovered that the determination of CD4 effector and memory fates after infection is regulated not only by initial signals from antigen and pathogen recognition, but also by a second round of such signals at a checkpoint during the effector response. Signals to effectors determine their subsequent fate, inducing further progression to tissue-restricted follicular helpers, cytotoxic CD4 effectors, and long-lived memory cells. The follicular helpers help the germinal center B-cell responses that give rise to high-affinity long-lived antibody responses and memory B cells that synergize with T-cell memory to provide robust long-lived protection. We postulate that inactivated vaccines do not provide extended signals from antigen and pathogen beyond a few days, and thus elicit ineffective CD4 T- and B-cell effector responses and memory. Defining the mechanisms that underlie effective responses should provide insights necessary to develop vaccine strategies that induce more effective and durable immunity.
Identifiants
pubmed: 33903157
pii: cshperspect.a038182
doi: 10.1101/cshperspect.a038182
pmc: PMC8559547
pii:
doi:
Substances chimiques
Influenza Vaccines
0
Pathogen-Associated Molecular Pattern Molecules
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R21 AI153120
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI046530
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI146532
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI118820
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007349
Pays : United States
Informations de copyright
Copyright © 2021 Cold Spring Harbor Laboratory Press; all rights reserved.
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