Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.
Eur J Immunol
; 52(7): 1171-1189, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35562849
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Common Variable Immunodeficiency
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Eur J Immunol
Year:
2022
Document type:
Article
Affiliation country: