Haematopoietic Stem Cell Transplantation Results in Extensive Remodelling of the Clonal T Cell Repertoire in Multiple Sclerosis.
T cell
TCR - T cell receptor
aHSCT
multiple sclerosis
public clonotypes
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
20
10
2021
accepted:
13
01
2022
entrez:
24
2
2022
pubmed:
25
2
2022
medline:
23
3
2022
Statut:
epublish
Résumé
Autologous haematopoietic stem cell transplantation (AHSCT) is a vital therapeutic option for patients with highly active multiple sclerosis (MS). Rates of remission suggest AHSCT is the most effective form of immunotherapy in controlling the disease. Despite an evolving understanding of the biology of immune reconstitution following AHSCT, the mechanism by which AHSCT enables sustained disease remission beyond the period of lymphopenia remains to be elucidated. Auto-reactive T cells are considered central to MS pathogenesis. Here, we analyse T cell reconstitution for 36 months following AHSCT in a cohort of highly active MS patients. Through longitudinal analysis of sorted naïve and memory T cell clones, we establish that AHSCT induces profound changes in the dominant T cell landscape of both CD4+ and CD8+ memory T cell clones. Lymphopenia induced homeostatic proliferation is followed by clonal attrition; with only 19% of dominant CD4 (p <0.025) and 13% of dominant CD8 (p <0.005) clones from the pre-transplant repertoire detected at 36 months. Recovery of a thymically-derived CD4 naïve T cell repertoire occurs at 12 months and is ongoing at 36 months, however diversity of the naïve populations is not increased from baseline suggesting the principal mechanism of durable remission from MS after AHSCT relates to depletion of putative auto-reactive clones. In a cohort of MS patients expressing the MS risk allele HLA DRB1*15:01, public clones are probed as potential biomarkers of disease. AHSCT appears to induce sustained periods of disease remission with dynamic changes in the clonal T cell repertoire out to 36 months post-transplant.
Identifiants
pubmed: 35197974
doi: 10.3389/fimmu.2022.798300
pmc: PMC8859174
doi:
Substances chimiques
Immunologic Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
798300Informations de copyright
Copyright © 2022 Massey, Jackson, Singh, Hughes, Withers, Ford, Khoo, Hendrawan, Zaunders, Charmeteau-De Muylder, Cheynier, Luciani, Ma, Moore and Sutton.
Déclaration de conflit d'intérêts
JMa and IS have received honoraria from Biogen, Roche, Sanofi Genzyme, Merck and Teva. Subsequent to involvement in the research, CF is now employed at BD Biosciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Brain. 2013 Sep;136(Pt 9):2888-903
pubmed: 23864273
Biol Blood Marrow Transplant. 2020 Jan;26(1):50-57
pubmed: 31525494
Eur J Immunol. 2014 Nov;44(11):3439-52
pubmed: 25103993
Curr Opin Immunol. 2007 Jun;19(3):294-300
pubmed: 17433874
Brain. 2004 May;127(Pt 5):996-1008
pubmed: 14985264
Genome Res. 2011 May;21(5):790-7
pubmed: 21349924
N Engl J Med. 2018 Jan 11;378(2):169-180
pubmed: 29320652
J Immunol. 2006 Sep 15;177(6):3893-902
pubmed: 16951352
Eur J Immunol. 2006 Mar;36(3):533-43
pubmed: 16506290
Nat Commun. 2016 Mar 23;7:11112
pubmed: 27005435
BMC Bioinformatics. 2015 May 28;16:175
pubmed: 26017500
Mult Scler. 2017 Feb;23(2):201-204
pubmed: 27207454
Nat Protoc. 2014 Jan;9(1):171-81
pubmed: 24385147
J Immunol. 2016 Jun 15;196(12):5005-13
pubmed: 27183615
Neurol Neuroimmunol Neuroinflamm. 2019 Nov 22;7(1):
pubmed: 31757815
J Immunol. 2014 Mar 15;192(6):2689-98
pubmed: 24510963
Bone Marrow Transplant. 2020 Feb;55(2):283-306
pubmed: 31558790
Phys Rev E. 2020 Jun;101(6-1):062414
pubmed: 32688532
Eur J Immunol. 2005 Nov;35(11):3332-42
pubmed: 16231285
Nat Rev Neurol. 2020 Jan;16(1):56-62
pubmed: 31649335
Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18691-6
pubmed: 17130450
Brain. 2018 Apr 1;141(4):1075-1084
pubmed: 29462277
J Clin Invest. 2007 Aug;117(8):2176-85
pubmed: 17627303
Nat Genet. 2013 Nov;45(11):1353-60
pubmed: 24076602
Lancet Neurol. 2020 Apr;19(4):307-316
pubmed: 32199096
Exp Mol Med. 2018 Mar 9;50(3):e456
pubmed: 29520112
Sci Rep. 2019 Jan 23;9(1):344
pubmed: 30674904
Philos Trans R Soc Lond B Biol Sci. 2015 Aug 19;370(1675):
pubmed: 26150657
Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9875-80
pubmed: 24941953
Nat Rev Immunol. 2008 Mar;8(3):231-8
pubmed: 18301425
J Neurol Neurosurg Psychiatry. 2019 May;90(5):514-521
pubmed: 30538138
Nucleic Acids Res. 2020 Jan 8;48(D1):D1057-D1062
pubmed: 31588507
Nucleic Acids Res. 2018 Jan 4;46(D1):D419-D427
pubmed: 28977646
Exp Neurol. 2014 Dec;262 Pt A:37-43
pubmed: 24792641
Drugs. 2018 Oct;78(15):1549-1566
pubmed: 30255442
PLoS Comput Biol. 2015 Nov 25;11(11):e1004503
pubmed: 26606115
J Clin Invest. 2014 Mar;124(3):1168-72
pubmed: 24531550
Blood. 2013 Jan 24;121(4):573-84
pubmed: 23160470
Nature. 2011 Aug 10;476(7359):214-9
pubmed: 21833088
J Exp Med. 2005 Mar 7;201(5):805-16
pubmed: 15738052
Nat Biotechnol. 2020 Oct;38(10):1194-1202
pubmed: 32341563
PLoS Comput Biol. 2020 Dec 9;16(12):e1008394
pubmed: 33296360
Front Immunol. 2020 Apr 09;11:559
pubmed: 32328061
J Immunol. 2017 Mar 15;198(6):2310-2319
pubmed: 28159903
Nat Rev Neurol. 2017 Jul;13(7):391-405
pubmed: 28621766
BMC Genomics. 2016 Jun 13;17:453
pubmed: 27297497
Immunol Cell Biol. 2003 Dec;81(6):487-95
pubmed: 14636246
Blood. 2009 Jan 22;113(4):769-74
pubmed: 18583570
Lancet Neurol. 2016 Feb;15(2):198-209
pubmed: 26724103
Methods Mol Biol. 2007;380:197-213
pubmed: 17876095
Exp Hematol. 2004 Oct;32(10):1010-22
pubmed: 15504556
Neurology. 2017 Mar 21;88(12):1197-1205
pubmed: 28228564
Ann Clin Transl Neurol. 2015 Jun;2(6):609-22
pubmed: 26125037
Brain. 2007 Nov;130(Pt 11):2789-99
pubmed: 17890278
Lancet Neurol. 2010 Apr;9(4):438-46
pubmed: 20298967
Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13139-44
pubmed: 25157137
Immunology. 2013 Oct;140(2):211-9
pubmed: 23721329
Brief Bioinform. 2018 Jul 20;19(4):554-565
pubmed: 28077404
Genome Med. 2015 May 28;7(1):49
pubmed: 26140055
JCI Insight. 2020 Jan 30;5(2):
pubmed: 31877116
Clin Exp Immunol. 2017 Sep;189(3):268-278
pubmed: 28498568
Am J Epidemiol. 2007 May 15;165(10):1097-109
pubmed: 17329717
AIDS. 2014 May 15;28(8):1101-13
pubmed: 24614087
Front Immunol. 2018 Feb 02;9:100
pubmed: 29456529
Blood Adv. 2017 Dec 20;1(27):2742-2755
pubmed: 29296926
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20200-5
pubmed: 24282306
Blood. 2016 Jan 7;127(1):91-101
pubmed: 26480932
J Exp Med. 2002 Jun 17;195(12):1523-32
pubmed: 12070280
Ann Clin Transl Neurol. 2016 Apr 20;3(6):422-33
pubmed: 27547770
Ann Neurol. 2013 Mar;73(3):341-54
pubmed: 23463494
EBioMedicine. 2021 Jun;68:103429
pubmed: 34127432
Nat Methods. 2014 Jun;11(6):653-5
pubmed: 24793455