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Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.
- Source :
-
European journal of immunology [Eur J Immunol] 2022 Jul; Vol. 52 (7), pp. 1171-1189. Date of Electronic Publication: 2022 May 29. - Publication Year :
- 2022
-
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.<br /> (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 52
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 35562849
- Full Text :
- https://doi.org/10.1002/eji.202149480