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Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.

Authors :
Milardi G
Di Lorenzo B
Gerosa J
Barzaghi F
Di Matteo G
Omrani M
Jofra T
Merelli I
Barcella M
Filippini M
Conti A
Ferrua F
Pozzo Giuffrida F
Dionisio F
Rovere-Querini P
Marktel S
Assanelli A
Piemontese S
Brigida I
Zoccolillo M
Cirillo E
Giardino G
Danieli MG
Specchia F
Pacillo L
Di Cesare S
Giancotta C
Romano F
Matarese A
Chetta AA
Trimarchi M
Laurenzi A
De Pellegrin M
Darin S
Montin D
Marinoni M
Dellepiane RM
Sordi V
Lougaris V
Vacca A
Melzi R
Nano R
Azzari C
Bongiovanni L
Pignata C
Cancrini C
Plebani A
Piemonti L
Petrovas C
Di Micco R
Ponzoni M
Aiuti A
Cicalese MP
Fousteri G
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