Long-term robustness of a T-cell system emerging from somatic rescue of a genetic block in T-cell development.
Adolescent
Biomarkers
Case-Control Studies
Cell Differentiation
/ genetics
Child
Clonal Evolution
/ genetics
Female
Flow Cytometry
Genetic Testing
Humans
Immunophenotyping
Killer Cells, Natural
/ immunology
Lymphopoiesis
/ genetics
Male
T-Lymphocyte Subsets
/ cytology
X-Linked Combined Immunodeficiency Diseases
/ genetics
Immunodeficiency
T cells
T-cell development
TCR diversity
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
14
05
2020
revised:
03
08
2020
accepted:
04
08
2020
pubmed:
26
8
2020
medline:
29
6
2021
entrez:
26
8
2020
Statut:
ppublish
Résumé
The potential of a single progenitor cell to establish and maintain long-term protective T-cell immunity in humans is unknown. For genetic disorders disabling T-cell immunity, somatic reversion was shown to support limited T-cell development attenuating the clinical phenotype. However, the cases reported so far deteriorated over time leaving unanswered the important question of long-term activity of revertant precursors and the robustness of the resulting T-cell system. We applied TCRβ-CDR3 sequencing and mass cytometry on serial samples of a now 18 year-old SCIDX1 patient with somatic reversion to analyse the longitudinal diversification and stability of a T-cell system emerging from somatic gene rescue. We detected close to 10 Genetic correction in the appropriate cell type, in our patient most likely in a T-cell biased self-renewing hematopoietic progenitor, can yield a diverse T-cell system that provides long-term repertoire stability, does not show evidence for progressive exhaustion and is capable of providing protective and regulated T-cell immunity for at least two decades. DFG EH 145/9-1, DFG SCHW 432/4-1 and the German Research Foundation under Germany's Excellence Strategy-EXC-2189-Project ID: 390939984.
Identifiants
pubmed: 32841837
pii: S2352-3964(20)30337-6
doi: 10.1016/j.ebiom.2020.102961
pmc: PMC7452388
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102961Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
Références
JCI Insight. 2018 Aug 9;3(15):
pubmed: 30089728
J Exp Med. 2012 Jul 30;209(8):1409-17
pubmed: 22778389
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1536-40
pubmed: 9990059
J Exp Med. 2000 Aug 21;192(4):557-64
pubmed: 10952725
J Immunol. 2014 Jun 1;192(11):5050-8
pubmed: 24771849
Nat Rev Immunol. 2001 Dec;1(3):200-8
pubmed: 11905829
J Immunol. 2004 Jan 15;172(2):864-70
pubmed: 14707057
Nature. 1988 Aug 4;334(6181):395-402
pubmed: 3043226
J Immunol. 2016 Jun 15;196(12):5005-13
pubmed: 27183615
Immunol Rev. 2010 Nov;238(1):126-37
pubmed: 20969589
Sci Immunol. 2016 Dec 16;1(6):
pubmed: 28783691
Nat Rev Immunol. 2016 Apr;16(4):234-46
pubmed: 26996199
Blood. 2009 Nov 5;114(19):4099-107
pubmed: 19706884
Blood. 2008 Nov 15;112(10):4090-7
pubmed: 18728247
Lancet. 2004 Dec 18-31;364(9452):2181-7
pubmed: 15610804
BMC Immunol. 2019 Jun 21;20(1):19
pubmed: 31226930
Eur J Immunol. 2007 Nov;37(11):3270-80
pubmed: 17935071
PLoS One. 2019 Mar 14;14(3):e0213684
pubmed: 30870493
Blood. 2020 Apr 9;135(15):1219-1231
pubmed: 32040546
Am J Med Genet A. 2017 Sep;173(9):2366-2372
pubmed: 28627729
Nat Commun. 2013;4:2680
pubmed: 24157944
Nat Rev Dis Primers. 2015 Oct 29;1:15061
pubmed: 27189259
N Engl J Med. 1996 Nov 21;335(21):1563-7
pubmed: 8900089
Sci Transl Med. 2011 Aug 24;3(97):97ra79
pubmed: 21865537
J Immunol. 2010 Nov 1;185(9):4993-7
pubmed: 20889548
Nature. 1984 May 24-30;309(5966):322-6
pubmed: 6328306
Cell Rep. 2018 Nov 27;25(9):2308-2316.e4
pubmed: 30485801
Nat Cell Biol. 2017 Apr;19(4):271-281
pubmed: 28319093
Arthritis Res Ther. 2015 May 23;17:132
pubmed: 26001779
Methods Mol Biol. 2012;882:569-604
pubmed: 22665256
Nat Commun. 2017 May 09;8:15183
pubmed: 28485371
Trends Immunol. 2014 Oct 8;35(12):581-590
pubmed: 25306219
J Exp Med. 2011 Feb 14;208(2):357-68
pubmed: 21262959
Mol Immunol. 1997 Oct;34(15):1067-82
pubmed: 9519765
Mol Ther. 2006 Oct;14(4):505-13
pubmed: 16905365
J Allergy Clin Immunol. 2017 Apr;139(4):1302-1310.e4
pubmed: 27658761
Nat Biotechnol. 2018 Dec 03;:
pubmed: 30531897
Nature. 2014 May 22;509(7501):465-70
pubmed: 24828041
J Mol Diagn. 2017 Sep;19(5):755-765
pubmed: 28826609
Nat Rev Genet. 2019 Oct;20(10):582-598
pubmed: 31186537
Scand J Immunol. 2012 Apr;75(4):436-44
pubmed: 22420532
Nature. 2018 Feb 1;554(7690):106-111
pubmed: 29298288
J Virol. 2015 Apr;89(8):4517-26
pubmed: 25653453
BMC Bioinformatics. 2017 Feb 27;18(1):129
pubmed: 28241742
Nature. 2018 Sep;561(7724):473-478
pubmed: 30185910
Nature. 2001 Nov 1;414(6859):105-11
pubmed: 11689955
Science. 1999 Oct 29;286(5441):958-61
pubmed: 10542151
Eur J Immunol. 2019 Mar;49(3):462-475
pubmed: 30578679
Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13139-44
pubmed: 25157137
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):274-8
pubmed: 10618408
Nature. 2017 Aug 24;548(7668):456-460
pubmed: 28813413
Genome Med. 2018 Sep 28;10(1):70
pubmed: 30261899
Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):E6020-7
pubmed: 26483497
Front Immunol. 2020 Jan 22;10:3039
pubmed: 32038613
N Engl J Med. 2014 Oct 9;371(15):1407-17
pubmed: 25295500
N Engl J Med. 2010 Nov 11;363(20):1918-27
pubmed: 21067383
Exp Gerontol. 2017 Oct 1;96:29-37
pubmed: 28535950