Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.
B cells
Common variable immunodeficiency
Immune aging
T follicular helper cells
T-cell exhaustion
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
08
02
2022
received:
29
06
2021
accepted:
09
05
2022
pubmed:
15
5
2022
medline:
14
7
2022
entrez:
14
5
2022
Statut:
ppublish
Résumé
Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were identified in four patients belonging to this group. Their blood lymphocytes showed shortened telomeres, while their cTfh were more prone to apoptosis. These data point toward a novel pathogenetic mechanism in CVID, whereby alterations in DNA repair and telomere elongation might predispose to antibody deficiency. A Th1, highly activated but exhausted and apoptotic cTfh phenotype was associated with this form of CVID.
Identifiants
pubmed: 35562849
doi: 10.1002/eji.202149480
pmc: PMC9542315
doi:
Substances chimiques
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1171-1189Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
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