Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2018

Open Access 01-12-2018 | Review

Modulation of T-cell responses by anti-tumor necrosis factor treatments in rheumatoid arthritis: a review

Authors: Jean-Luc Davignon, Benjamin Rauwel, Yannick Degboé, Arnaud Constantin, Jean-Fredéric Boyer, Andrey Kruglov, Alain Cantagrel

Published in: Arthritis Research & Therapy | Issue 1/2018

Login to get access

Abstract

Tumor necrosis factor (TNF) is a pleiotropic cytokine involved in many aspects of immune regulation. Anti-TNF biological therapy has been considered a breakthrough in the treatment of chronic autoimmune diseases, such as rheumatoid arthritis (RA). In this review, because of the major involvement of T cells in RA pathogenesis, we discuss the effects of anti-TNF biotherapy on T-cell responses in RA patients. We also outline the potential fields for future research in the area of anti-TNF therapy in RA.
This could be useful to better understand the therapeutic efficiency and the side effects that are encountered in RA patients. Better targeting of T cells in RA could help set more specific anti-TNF strategies and develop prediction tools for response.
Literature
1.
Feldmann M, Maini RN. Anti-TNF therapy, from rationale to standard of care: what lessons has it taught us? J Immunol. 2010;185:791–4.CrossRefPubMed
2.
Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. 2016;12:49–62.CrossRefPubMed
3.
Horiuchi T, Mitoma H, Harashima S, Tsukamoto H, Shimoda T. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford). 2010;49:1215–28.CrossRef
4.
McCann FE, Perocheau DP, Ruspi G, Blazek K, Davies ML, Feldmann M, et al. Selective tumor necrosis factor receptor I blockade is antiinflammatory and reveals immunoregulatory role of tumor necrosis factor receptor II in collagen-induced arthritis: immunoregulatory role of TNFRII in CIA. Arthritis Rheumatol. 2014;66:2728–38.CrossRefPubMed
5.
Benson RA, McInnes IB, Garside P, Brewer JM. Model answers: rational application of murine models in arthritis research. Eur J Immunol. 2018;48:32–8.CrossRefPubMed
6.
Gourraud P-A, Dieudé P, Boyer J-F, Nogueira L, Cambon-Thomsen A, Mazières B, et al. A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis. Arthritis Res Ther. 2007;9:R27.CrossRefPubMedCentralPubMed
7.
8.
Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R, Steinfeld S, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003;349:1907–15.CrossRefPubMed
9.
10.
Baseta JG, Stutman O. TNF regulates thymocyte production by apoptosis and proliferation of the triple negative (CD3-CD4-CD8-) subset. J Immunol. 2000;165:5621–30.CrossRefPubMed
11.
Guevara Patiño JA, Ivanov VN, Lacy E, Elkon KB, Marino MW, Nikolic-Zugić J. TNF-alpha is the critical mediator of the cyclic AMP-induced apoptosis of CD8+4+ double-positive thymocytes. J Immunol. 2000;164:1689–94.CrossRefPubMed
12.
13.
Anolik JH, Ravikumar R, Barnard J, Owen T, Almudevar A, Milner ECB, et al. Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks. J Immunol. 2008;180:688–92.CrossRefPubMed
14.
Tumanov AV, Grivennikov SI, Kruglov AA, Shebzukhov YV, Koroleva EP, Piao Y, et al. Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs. Blood. 2010;116:3456–64.CrossRefPubMedCentralPubMed
15.
16.
Suresh M, Singh A, Fischer C. Role of tumor necrosis factor receptors in regulating CD8 T-cell responses during acute lymphocytic choriomeningitis virus infection. J Virol. 2005;79:202–13.CrossRefPubMedCentralPubMed
17.
Jaczewska J, Abdulreda MH, Yau CY, Schmitt MM, Schubert I, Berggren P-O, et al. TNF-α and IFN-γ promote lymphocyte adhesion to endothelial junctional regions facilitating transendothelial migration. J Leukoc Biol. 2014;95:265–74.CrossRefPubMedCentralPubMed
18.
Kim EY, Priatel JJ, Teh S-J, Teh H-S. TNF receptor type 2 (p75) functions as a costimulator for antigen-driven T cell responses in vivo. J Immunol. 2006;176:1026–35.CrossRefPubMed
19.
Chen X, Oppenheim JJ. Contrasting effects of TNF and anti-TNF on the activation of effector T cells and regulatory T cells in autoimmunity. FEBS Lett. 2011;585:3611–8.CrossRefPubMedCentralPubMed
20.
Érsek B, Molnár V, Balogh A, Matkó J, Cope AP, Buzás EI, et al. CD3ζ-chain expression of human T lymphocytes is regulated by TNF via Src-like adaptor protein-dependent proteasomal degradation. J Immunol. 2012;189:1602–10.CrossRefPubMed
21.
Chimenti MS, Tucci P, Candi E, Perricone R, Melino G, Willis AE. Metabolic profiling of human CD4+ cells following treatment with methotrexate and anti-TNF-α infliximab. Cell Cycle. 2013;12:3025–36.CrossRefPubMedCentralPubMed
22.
Cope AP, Londei M, Chu NR, Cohen SB, Elliott MJ, Brennan FM, et al. Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis. J Clin Invest. 1994;94:749–60.CrossRefPubMedCentralPubMed
23.
Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S-I, Kikuchi Y, et al. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology. 2005;128:376–92.CrossRefPubMed
24.
Ueda N, Tsukamoto H, Mitoma H, Ayano M, Tanaka A, Ohta S, et al. The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α. Inflamm Bowel Dis. 2013;19:1224–31.CrossRefPubMed
25.
Toubi E, Kessel A, Mahmudov Z, Hallas K, Rozenbaum M, Rosner I. Increased spontaneous apoptosis of CD4+CD25+ T cells in patients with active rheumatoid arthritis is reduced by infliximab. Ann N Y Acad Sci. 2005;1051:506–14.CrossRefPubMed
26.
Aerts NE, De Knop KJ, Leysen J, Ebo DG, Bridts CH, Weyler JJ, et al. Increased IL-17 production by peripheral T helper cells after tumour necrosis factor blockade in rheumatoid arthritis is accompanied by inhibition of migration-associated chemokine receptor expression. Rheumatology (Oxford). 2010;49:2264–72.CrossRef
27.
Talotta R, Berzi A, Atzeni F, Batticciotto A, Clerici M, Sarzi-Puttini P, et al. Paradoxical expansion of Th1 and Th17 lymphocytes in rheumatoid arthritis following infliximab treatment: a possible explanation for a lack of clinical response. J Clin Immunol. 2015;35:550–7.CrossRefPubMed
28.
Szalay B, Vásárhelyi B, Cseh A, Tulassay T, Deák M, Kovács L, et al. The impact of conventional DMARD and biological therapies on CD4+ cell subsets in rheumatoid arthritis: a follow-up study. Clin Rheumatol. 2014;33:175–85.CrossRefPubMed
29.
Dulic S, Vásárhelyi Z, Sava F, Berta L, Szalay B, Toldi G, et al. T-cell subsets in rheumatoid arthritis patients on long-term anti-TNF or IL-6 receptor blocker therapy. Mediat Inflamm. 2017;2017:6894374.CrossRef
30.
Hull DN, Cooksley H, Chokshi S, Williams RO, Abraham S, Taylor PC. Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis. Arthritis Res Ther. 2016;18:303.CrossRefPubMedCentralPubMed
31.
Cosmi L, Liotta F, Maggi E, Romagnani S, Annunziato F. Th17 and non-classic Th1 cells in chronic inflammatory disorders: two sides of the same coin. Int Arch Allergy Immunol. 2014;164:171–7.CrossRefPubMed
32.
Chen D-Y, Chen Y-M, Chen H-H, Hsieh C-W, Lin C-C, Lan J-L. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy. Arthritis Res Ther. 2011;13:R126.CrossRefPubMedCentralPubMed
33.
Alzabin S, Abraham SM, Taher TE, Palfreeman A, Hull D, McNamee K, et al. Incomplete response of inflammatory arthritis to TNFα blockade is associated with the Th17 pathway. Ann Rheum Dis. 2012;71:1741–8.CrossRefPubMed
34.
McGovern JL, Nguyen DX, Notley CA, Mauri C, Isenberg DA, Ehrenstein MR. Th17 cells are restrained by Treg cells via the inhibition of interleukin-6 in patients with rheumatoid arthritis responding to anti-tumor necrosis factor antibody therapy. Arthritis Rheum. 2012;64:3129–38.CrossRefPubMed
35.
Evans HG, Roostalu U, Walter GJ, Gullick NJ, Frederiksen KS, Roberts CA, et al. TNF-α blockade induces IL-10 expression in human CD4+ T cells. Nat Commun. 2014;5:3199.CrossRefPubMed
36.
Aerts NE, Ebo DG, Bridts CH, Stevens WJ, De Clerck LS. T cell signal transducer and activator of transcription (STAT) 4 and 6 are affected by adalimumab therapy in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28:208–14.PubMed
37.
Conrad C, Di Domizio J, Mylonas A, Belkhodja C, Demaria O, Navarini AA, et al. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nat Commun. 2018;9:25.CrossRefPubMedCentralPubMed
38.
Wendling D, Prati C. Paradoxical effects of anti-TNF-α agents in inflammatory diseases. Expert Rev Clin Immunol. 2014;10:159–69.CrossRefPubMed
39.
Rao DA, Gurish MF, Marshall JL, Slowikowski K, Fonseka CY, Liu Y, et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature. 2017;542:110–4.CrossRefPubMedCentralPubMed
40.
Chen X, Wu X, Zhou Q, Howard OMZ, Netea MG, Oppenheim JJ. TNFR2 is critical for the stabilization of the CD4+Foxp3+ regulatory T cell phenotype in the inflammatory environment. J Immunol. 2013;190:1076–84.CrossRefPubMed
41.
Byng-Maddick R, Ehrenstein MR. The impact of biological therapy on regulatory T cells in rheumatoid arthritis. Rheumatology (Oxford). 2015;54:768–75.CrossRef
42.
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.CrossRefPubMed
43.
Zaragoza B, Chen X, Oppenheim JJ, Baeyens A, Gregoire S, Chader D, et al. Suppressive activity of human regulatory T cells is maintained in the presence of TNF. Nat Med. 2016;22:16–7.CrossRefPubMedCentralPubMed
44.
Nadkarni S, Mauri C, Ehrenstein MR. Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med. 2007;204:33–9.CrossRefPubMedCentralPubMed
45.
Nguyen DX, Ehrenstein MR. Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RII binding in rheumatoid arthritis. J Exp Med. 2016;213:1241–53.CrossRefPubMedCentralPubMed
46.
Rossol M, Meusch U, Pierer M, Kaltenhäuser S, Häntzschel H, Hauschildt S, et al. Interaction between transmembrane TNF and TNFR1/2 mediates the activation of monocytes by contact with T cells. J Immunol. 2007;179:4239–48.CrossRefPubMed
47.
Parry SL, Sebbag M, Feldmann M, Brennan FM. Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. J Immunol. 1997;158:3673–81.PubMed
48.
Wallis RS. Infectious complications of tumor necrosis factor blockade. Curr Opin Infect Dis. 2009;22:403–9.CrossRefPubMed
49.
Bruns H, Meinken C, Schauenberg P, Härter G, Kern P, Modlin RL, et al. Anti-TNF immunotherapy reduces CD8+ T cell-mediated antimicrobial activity against Mycobacterium tuberculosis in humans. J Clin Invest. 2009;119:1167–77.CrossRefPubMedCentralPubMed
50.
Hamdi H, Mariette X, Godot V, Weldingh K, Hamid AM, Prejean M-V, et al. Inhibition of anti-tuberculosis T-lymphocyte function with tumour necrosis factor antagonists. Arthritis Res Ther. 2006;8:R114.CrossRefPubMedCentralPubMed
51.
Slifman NR, Gershon SK, Lee J-H, Edwards ET, Braun MM. Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents. Arthritis Rheum. 2003;48:319–24.CrossRefPubMed
52.
Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol. 2002;2:251–62.CrossRefPubMed
53.
54.
Davignon J-L, Boyer J-F, Jamard B, Nigon D, Constantin A, Cantagrel A. Maintenance of cytomegalovirus-specific CD4pos T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments. Arthritis Res Ther. 2010;12:R142.CrossRefPubMedCentralPubMed
55.
Carroll MB, Bond MI. Use of tumor necrosis factor-alpha inhibitors in patients with chronic hepatitis B infection. Semin Arthritis Rheum. 2008;38:208–17.CrossRefPubMed
56.
Nard FD, Todoerti M, Grosso V, Monti S, Breda S, Rossi S, et al. Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: extending perspective from old to newer drugs. World J Hepatol. 2015;7:344–61.CrossRefPubMedCentralPubMed
57.
Viganò M, Degasperi E, Aghemo A, Lampertico P, Colombo M. Anti-TNF drugs in patients with hepatitis B or C virus infection: safety and clinical management. Expert Opin Biol Ther. 2012;12:193–207.CrossRefPubMed
58.
Balog A, Klausz G, Gál J, Molnár T, Nagy F, Ocsovszky I, et al. Investigation of the prognostic value of TNF-alpha gene polymorphism among patients treated with infliximab, and the effects of infliximab therapy on TNF-alpha production and apoptosis. Pathobiology. 2004;71:274–80.CrossRefPubMed
59.
Unutmaz D, Pileri P, Abrignani S. Antigen-independent activation of naive and memory resting T cells by a cytokine combination. J Exp Med. 1994;180:1159–64.CrossRefPubMed
60.
Aversa G, Punnonen J, de Vries JE. The 26-kD transmembrane form of tumor necrosis factor alpha on activated CD4+ T cell clones provides a costimulatory signal for human B cell activation. J Exp Med. 1993;177:1575–85.CrossRefPubMed
61.
Kaine JL, Kivitz AJ, Birbara C, Luo AY. Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab. J Rheumatol. 2007;34:272–9.PubMed
62.
Friedman MA, Winthrop KL. Vaccines and disease-modifying antirheumatic drugs: practical implications for the rheumatologist. Rheum Dis Clin N Am. 2017;43:1–13.CrossRef
63.
van Schouwenburg PA, Rispens T, Wolbink GJ. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol. 2013;9:164–72.CrossRefPubMed
64.
Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis. 2001;60:729–35.CrossRefPubMedCentralPubMed
65.
Drutskaya MS, Efimov GA, Kruglov AA, Nedospasov SA. Can we design a better anti-cytokine therapy? J Leukoc Biol. 2017;102:783–90.CrossRefPubMed
66.
Nesbitt A, Fossati G, Bergin M, Stephens P, Stephens S, Foulkes R, et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm Bowel Dis. 2007;13:1323–32.CrossRefPubMed
Metadata
Title
Modulation of T-cell responses by anti-tumor necrosis factor treatments in rheumatoid arthritis: a review
Authors
Jean-Luc Davignon
Benjamin Rauwel
Yannick Degboé
Arnaud Constantin
Jean-Fredéric Boyer
Andrey Kruglov
Alain Cantagrel
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2018
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-018-1725-6

Other articles of this Issue 1/2018

Arthritis Research & Therapy 1/2018 Go to the issue

Research article

Autoimmune reactivity to malondialdehyde adducts in systemic lupus erythematosus is associated with disease activity and nephritis

Research article

Methotrexate upregulates circadian transcriptional factors PAR bZIP to induce apoptosis on rheumatoid arthritis synovial fibroblasts

Research article

Serum biomarker for diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis

Research article

Highly selective inhibition of Bruton’s tyrosine kinase attenuates skin and brain disease in murine lupus

Research article

The relationship between ferritin and urate levels and risk of gout

Research article

Tophus resolution in patients with chronic refractory gout who have persistent urate-lowering responses to pegloticase

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits