CD4+ Memory Stem T Cells Recognizing Citrullinated Epitopes Are Expanded in Patients With Rheumatoid Arthritis and Sensitive to Tumor Necrosis Factor Blockade.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
24
08
2018
accepted:
31
10
2019
pubmed:
5
11
2019
medline:
21
7
2020
entrez:
5
11
2019
Statut:
ppublish
Résumé
Memory stem T (Tscm) cells are long-lived, self-renewing T cells that play a relevant role in immunologic memory. This study was undertaken to investigate whether Tscm cells accumulate in rheumatoid arthritis (RA). The polarization and differentiation profiles of circulating T cells were assessed by flow cytometry. Antigen-specific T cells were characterized by staining with major histocompatibility complex class II tetramers. The T cell receptor (TCR) repertoire was analyzed by high-throughput sequencing using an unbiased RNA-based approach in CD4+ T cell subpopulations sorted by fluorescence-activated cell sorting. We analyzed the dynamics of circulating Tscm cells (identified as CD45RA+CD62L+CD95+ T cells) by flow cytometry in 27 RA patients, 16 of whom were also studied during treatment with the anti-tumor necrosis factor (anti-TNF) agent etanercept. Age-matched healthy donors were used as controls. CD4+ Tscm cells were selectively and significantly expanded in RA patients in terms of frequency and absolute numbers, and significantly contracted upon anti-TNF treatment. Expanded CD4+ Tscm cells displayed a prevalent Th17 phenotype and a skewed TCR repertoire in RA patients, with the 10 most abundant clones representing up to 53.7% of the detected sequences. CD4+ lymphocytes specific for a citrullinated vimentin (Cit-vimentin) epitope were expanded in RA patients with active disease. Tscm cells accounted for a large fraction of Cit-vimentin-specific CD4+ cells. Our results indicate that Tscm cells, including expanded clones specific for relevant autoantigens, accumulate in RA patients not exposed to biologic agents, and might be involved in the natural history of the disease. Further analysis of Tscm cell dynamics in autoimmune disorders may have implications for the design and efficacy assessment of innovative therapies.
Substances chimiques
Antirheumatic Agents
0
Epitopes, T-Lymphocyte
0
Tumor Necrosis Factor Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
565-575Informations de copyright
© 2019, American College of Rheumatology.
Références
Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, et al. A human memory T cell subset with stem cell-like properties. Nat Med 2011;17:1290-7.
Gattinoni L, Speiser DE, Lichterfeld M, Bonini C. T memory stem cells in health and disease. Nat Med 2017;23:18-27.
Biasco L, Scala S, Basso Ricci L, Dionisio F, Baricordi C, Calabria A, et al. In vivo tracking of T cells in humans unveils decade-long survival and activity of genetically modified T memory stem cells. Sci Transl Med 2015;7:273ra13.
Cieri N, Camisa B, Cocchiarella F, Forcato M, Oliveira G, Provasi E, et al. IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood 2013;121: 573-84.
Oliveira G, Ruggiero E, Stanghellini MT, Cieri N, D'Agostino M, Fronza R, et al. Tracking genetically engineered lymphocytes long-term reveals the dynamics of T cell immunological memory. Sci Transl Med 2015;7:317ra198.
Xu Y, Zhang M, Ramos CA, Durett A, Liu E, Dakhova O, et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood 2014;123:3750-9.
Fuertes-Marraco SA, Soneson C, Cagnon L, Gannon PO, Allard M, Abed Maillard S, et al. Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination. Sci Transl Med 2015;7:282ra48.
Zhang Y, Joe G, Hexner E, Zhu J, Emerson SG. Host-reactive CD8+ memory stem cells in graft-versus-host disease. Nat Med 2005;11:1299-305.
Cieri N, Oliveira G, Greco R, Forcato M, Taccioli C, Cianciotti B, et al. Generation of human memory stem T cells upon haploidentical T-replete hematopoietic stem cell transplantation. Blood 2015;125:2865-74.
Hosokawa K, Muranski P, Feng X, Townsley DM, Liu B, Knickelbein J, et al. Memory stem T cells in autoimmune disease: high frequency of circulating CD8+ memory stem cells in acquired aplastic anemia. J Immunol 2016;196:1568-78.
Vignali D, Cantarelli E, Bordignon C, Canu A, Citro A, Annoni A, et al. Detection and characterization of CD8+ autoreactive memory stem T cells in patients with type 1 diabetes. Diabetes 2018;67:936-45.
McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet 2017;389:2328-37.
Malmström V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting [review]. Nat Rev Immunol 2017;17:60-75.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.
Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44-8.
Landais E, Saulquin X, Scotet E, Trautmann L, Peyrat MA, Yates JL, et al. Direct killing of Epstein-Barr virus (EBV)-infected B cells by CD4 T cells directed against the EBV lytic protein BHRF1. Blood 2004;103:1408-16.
Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol 2003;171:538-41.
Jabbari A, Harty JT. Simultaneous assessment of antigen-stimulated cytokine production and memory subset composition of memory CD8 T cells. J Immunol 2006;313:161-8.
Bolotin DA, Mamedov IZ, Britanova OV, Zvyagin IV, Shagin D, Ustyugova SV, et al. Next generation sequencing for TCR repertoire profiling: platform-specific features and correction algorithms. Eur J Immunol 2012;42:3073-83.
Ruggiero E, Nicolay JP, Fronza R, Arens A, Paruzynski A, Nowrouzi A, et al. High-resolution analysis of the human T-cell receptor repertoire. Nat Commun 2015;6:8081.
Bolotin DA, Poslavsky S, Mitrophanov I, Shugay M, Mamedov IZ, Putintseva EV, et al. MiXCR: software for comprehensive adaptive immunity profiling [letter]. Nat Methods 2015;12:380-1.
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365:2205-19.
Snir O, Rieck M, Gebe JA, Yue BB, Rawlings CA, Nepom G, et al. Identification and functional characterization of T cells reactive to citrullinated vimentin in HLA-DRB1*0401-positive humanized mice and rheumatoid arthritis patients. Arthritis Rheum 2011;63:2873-83.
Buzon MJ, Sun H, Li C, Shaw A, Seiss K, Ouyang Z, et al. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med 2014;20:139-142.
Mateus J, Lasso P, Pavia P, Rosas F, Roa N, Valencia-Hernández CA, et al. Low frequency of circulating CD8+ T stem cell memory cells in chronic chagasic patients with severe forms of the disease. PLoS Negl Trop Dis 2015;9:e3432.
Mpande CA, Dintwe OB, Musvosvi M, Mabwe S, Bilek N, Hatherill M, et al. Functional, antigen-specific stem cell memory (TSCM) CD4+ T cells are induced by human mycobacterium tuberculosis infection. Front Immunol 2018;9:324.
Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, et al. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 2015;125:2855-64.
Nagai Y, Kawahara M, Hishizawa M, Shimazu Y, Sugino N, Fujii S, et al. T memory stem cells are the hierarchical apex of adult T-cell leukemia. Blood 2015;125:3527-35.
Lee YJ, Park JA, Kwon H, Choi YS, Jung KC, Park SH, et al. Role of stem cell-like memory T cells in systemic lupus erythematosus. Arthritis Rheumatol 2018;70:1459-69.
Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, et al. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 2007;204:2803-12.
Van den Berg WB, McInnes IB. Th17 cells and IL-17 A-focus on immunopathogenesis and immunotherapeutics. Semin Arthritis Rheum 2013;43:158-70.
Nie H, Zheng Y, Li R, Guo TB, He D, Fang L, et al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis. Nat Med 2013;19:322-8.
Faustman D, Davis M. TNF receptor 2 pathway: drug target for autoimmune diseases. Nat Rev Drug Discov 2010;9:482-93.
McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007;7:429-42.
Lugli E, Dominguez MH, Gattinoni L, Chattopadhyay PK, Bolton DL, Song K, et al. Superior T memory stem cell persistence supports long-lived T cell memory. J Clin Invest 2013;123:594-99.