368
Views
27
CrossRef citations to date
0
Altmetric
Review

The role of T regulatory cells in immunopathogenesis of myasthenia gravis: implications for therapeutics

, , &

References

  • Cavalcante P, Bernasconi P, Mantegazza R. Autoimmune mechanisms in myasthenia gravis. Curr Opin Neurol 2012;25(5):621-9
  • Masuda M, Matsumoto M, Tanaka S, et al. Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients. J Neuroimmunol 2010;225(1-2):123-31
  • Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 2010;28:445-89
  • Schmidlin H, Diehl SA, Blom B. New insights into the regulation of human B-cell differentiation. Trends Immunol 2009;30(6):277-85
  • Shin DS, Jordan A, Basu S, et al. Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms. EMBO Rep 2014;15(9):991-9
  • Lim HW, Hillsamer P, Banham AH, et al. Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J Immunol 2005;175(7):4180-3
  • Liu R, Hao J, Dayao CS, et al. T-bet deficiency decreases susceptibility to experimental myasthenia gravis. Exp Neurol 2009;220(2):366-73
  • Gradolatto A, Nazzal D, Truffault F, et al. Both Treg cells and Tconv cells are defective in the Myasthenia gravis thymus: roles of IL-17 and TNF-alpha. J Autoimmun 2014;52:53-63
  • Berrih-Aknin S, Le Panse R. Myasthenia gravis: a comprehensive review of immune dysregulation and etiological mechanisms. J Autoimmun 2014;52:90-100
  • Thiruppathi M, Rowin J, Ganesh B, et al. Impaired regulatory function in circulating CD4(+)CD25(high)CD127(low/-) T cells in patients with myasthenia gravis. Clin Immunol 2012;145(3):209-23
  • Luther C, Adamopoulou E, Stoeckle C, et al. Prednisolone treatment induces tolerogenic dendritic cells and a regulatory milieu in myasthenia gravis patients. J Immunol 2009;183(2):841-8
  • Balandina A, Lecart S, Dartevelle P, et al. Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 2005;105(2):735-41
  • Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 2009;8(5):475-90
  • Farrugia ME, Vincent A. Autoimmune mediated neuromuscular junction defects. Curr Opin Neurol 2010;23(5):489-95
  • Tuzun E, Christadoss P. Complement associated pathogenic mechanisms in myasthenia gravis. Autoimmun Rev 2013;12(9):904-11
  • Le Panse R, Berrih-Aknin S. Autoimmune myasthenia gravis: autoantibody mechanisms and new developments on immune regulation. Curr Opin Neurol 2013;26(5):569-76
  • Gilhus NE. Myasthenia and the neuromuscular junction. Curr Opin Neurol 2012;25(5):523-9
  • Higuchi O, Hamuro J, Motomura M, et al. Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol 2011;69(2):418-22
  • Marx A, Pfister F, Schalke B, et al. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev 2013;12(9):875-84
  • Alahgholi-Hajibehzad M, Yilmaz V, Gulsen-Parman Y, et al. Association of HLA-DRB1 *14, -DRB1 *16 and -DQB1 *05 with MuSK-myasthenia gravis in patients from Turkey. Hum Immunol 2013;74(12):1633-5
  • Renton AE, Pliner HA, Provenzano C, et al. A Genome-wide Association Study of Myasthenia Gravis. JAMA Neurol 2015;72(4):396-404
  • Marx A, Willcox N, Leite MI, et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity 2010;43(5-6):413-27
  • Verschuuren JJ, Huijbers MG, Plomp JJ, et al. Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4. Autoimmun Rev 2013;12(9):918-23
  • Zivkovic SA, Clemens PR, Lacomis D. Characteristics of late-onset myasthenia gravis. J Neurol 2012;259(10):2167-71
  • Pedersen EG, Hallas J, Hansen K, et al. Late-onset myasthenia not on the increase: a nationwide register study in Denmark, 1996-2009. Eur J Neurol 2013;20(2):309-14
  • Vrolix K, Fraussen J, Molenaar PC, et al. The auto-antigen repertoire in myasthenia gravis. Autoimmunity 2010;43(5-6):380-400
  • Zhang B, Tzartos JS, Belimezi M, et al. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol 2012;69(4):445-51
  • Maggi L, Andreetta F, Antozzi C, et al. Thymoma-associated myasthenia gravis: outcome, clinical and pathological correlations in 197 patients on a 20-year experience. J Neuroimmunol 2008;201-202:237-44
  • Metzger TC, Anderson MS. Control of central and peripheral tolerance by Aire. Immunol Rev 2011;241(1):89-103
  • Hohlfeld R, Wekerle H. Reflections on the “intrathymic pathogenesis” of myasthenia gravis. J Neuroimmunol 2008;201-202:21-7
  • Huang GZ, Lo YL. Correlation between acetylcholine receptor antibody levels and thymic pathology in myasthenia gravis: a review. J Clin Neuromuscul Dis 2013;14(4):209-17
  • Le Panse R, Bismuth J, Cizeron-Clairac G, et al. Thymic remodeling associated with hyperplasia in myasthenia gravis. Autoimmunity 2010;43(5-6):401-12
  • Marx A, Hohenberger P, Hoffmann H, et al. The autoimmune regulator AIRE in thymoma biology: autoimmunity and beyond. J Thorac Oncol 2010;5(10 Suppl 4):S266-72
  • Scarpino S, Di Napoli A, Stoppacciaro A, et al. Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas. Clin Exp Immunol 2007;149(3):504-12
  • Weiss JM, Cufi P, Bismuth J, et al. SDF-1/CXCL12 recruits B cells and antigen-presenting cells to the thymus of autoimmune myasthenia gravis patients. Immunobiology 2013;218(3):373-81
  • Berrih-Aknin S, Ruhlmann N, Bismuth J, et al. CCL21 overexpressed on lymphatic vessels drives thymic hyperplasia in myasthenia. Ann Neurol 2009;66(4):521-31
  • Weiss JM, Cufi P, Le Panse R, et al. The thymus in autoimmune Myasthenia Gravis: Paradigm for a tertiary lymphoid organ. Rev Neurol (Paris) 2013;169(8-9):640-9
  • Gradolatto A, Nazzal D, Foti M, et al. Defects of immunoregulatory mechanisms in myasthenia gravis: role of IL-17. Ann N Y Acad Sci 2012;1274:40-7
  • Schmitt EG, Williams CB. Generation and function of induced regulatory T cells. Front Immunol 2013;4:152
  • Liu Y, Lan Q, Lu L, et al. Phenotypic and functional characteristic of a newly identified CD8+ Foxp3- CD103+ regulatory T cells. J Mol Cell Biol 2014;6(1):81-92
  • Varthaman A, Khallou-Laschet J, Clement M, et al. Control of T cell reactivation by regulatory Qa-1-restricted CD8+ T cells. J Immunol 2010;184(12):6585-91
  • Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012;30:531-64
  • Mahmud SA, Manlove LS, Schmitz HM, et al. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat Immunol 2014;15(5):473-81
  • Bettini ML, Vignali DA. Development of thymically derived natural regulatory T cells. Ann N Y Acad Sci 2010;1183:1-12
  • Schmetterer KG, Neunkirchner A, Pickl WF. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J 2012;26(6):2253-76
  • Yu N, Li X, Song W, et al. CD4(+)CD25 (+)CD127 (low/-) T cells: a more specific Treg population in human peripheral blood. Inflammation 2012;35(6):1773-80
  • Walker LS, Sansom DM. Confusing signals: Recent progress in CTLA-4 biology. Trends Immunol 2015;36(2):63-70
  • Delgoffe GM, Woo SR, Turnis ME, et al. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature 2013;501(7466):252-6
  • Kmieciak M, Gowda M, Graham L, et al. Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function. J Transl Med 2009;7:89
  • Kubach J, Lutter P, Bopp T, et al. Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function. Blood 2007;110(5):1550-8
  • Thornton AM, Korty PE, Tran DQ, et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol 2010;184(7):3433-41
  • Akimova T, Beier UH, Wang L, et al. Helios expression is a marker of T cell activation and proliferation. PLoS ONE 2011;6(8):e24226
  • Gregori S, Goudy KS, Roncarolo MG. The cellular and molecular mechanisms of immuno-suppression by human type 1 regulatory T cells. Front Immunol 2012;3:30
  • Weiner HL, da Cunha AP, Quintana F, et al. Oral tolerance. Immunol Rev 2011;241(1):241-59
  • Matheu MP, Othy S, Greenberg ML, et al. Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming. Nat Commun 2015;6:6219
  • Choi BD, Gedeon PC, Herndon JE2nd, et al. Human regulatory T cells kill tumor cells through granzyme-dependent cytotoxicity upon retargeting with a bispecific antibody. Cancer Immunol Res 2013;1(3):163
  • Sega EI, Leveson-Gower DB, Florek M, et al. Role of lymphocyte activation gene-3 (Lag-3) in conventional and regulatory T cell function in allogeneic transplantation. PLoS One 2014;9(1):e86551
  • Klein M, Vaeth M, Scheel T, et al. Repression of cyclic adenosine monophosphate upregulation disarms and expands human regulatory T cells. J Immunol 2012;188(3):1091-7
  • Peres RS, Liew FY, Talbot J, et al. Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis. Proc Natl Acad Sci USA 2015;112(8):2509-14
  • Yan Y, Zhang GX, Gran B, et al. IDO upregulates regulatory T cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. J Immunol 2010;185(10):5953-61
  • Hofer T, Krichevsky O, Altan-Bonnet G. Competition for IL-2 between Regulatory and Effector T Cells to Chisel Immune Responses. Front Immunol 2012;3:268
  • Fuchs S, Aricha R, Reuveni D, et al. Experimental Autoimmune Myasthenia Gravis (EAMG): from immunochemical characterization to therapeutic approaches. J Autoimmun 2014;54:51-9
  • Souroujon MC, Aricha R, Feferman T, et al. Regulatory T cell-based immunotherapies in experimental autoimmune myasthenia gravis. Ann N Y Acad Sci 2012;1274:120-6
  • Gertel-Lapter S, Mizrachi K, Berrih-Aknin S, et al. Impairment of regulatory T cells in myasthenia gravis: studies in an experimental model. Autoimmun Rev 2013;12(9):894-903
  • Aricha R, Feferman T, Fuchs S, et al. Ex vivo generated regulatory T cells modulate experimental autoimmune myasthenia gravis. J Immunol 2008;180(4):2132-9
  • Nessi V, Nava S, Ruocco C, et al. Naturally occurring CD4+CD25+ regulatory T cells prevent but do not improve experimental myasthenia gravis. J Immunol 2010;185(9):5656-67
  • Schwarz A, Schumacher M, Pfaff D, et al. Fine-tuning of regulatory T cell function: the role of calcium signals and naive regulatory T cells for regulatory T cell deficiency in multiple sclerosis. J Immunol 2013;190(10):4965-70
  • Soler DC, Sugiyama H, Young AB, et al. Psoriasis patients exhibit impairment of the high potency CCR5(+) T regulatory cell subset. Clin Immunol 2013;149(1):111-18
  • Haseda F, Imagawa A, Murase-Mishiba Y, et al. CD4(+) CD45RA(-) FoxP3high activated regulatory T cells are functionally impaired and related to residual insulin-secreting capacity in patients with type 1 diabetes. Clin Exp Immunol 2013;173(2):207-16
  • Huang YM, Pirskanen R, Giscombe R, et al. Circulating CD4+CD25+ and CD4+CD25+ T cells in myasthenia gravis and in relation to thymectomy. Scand J Immunol 2004;59(4):408-14
  • Sun Y, Qiao J, Lu CZ, et al. Increase of circulating CD4+CD25+ T cells in myasthenia gravis patients with stability and thymectomy. Clin Immunol 2004;112(3):284-9
  • Fattorossi A, Battaglia A, Buzzonetti A, et al. Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment. Immunology 2005;116(1):134-41
  • Li X, Xiao BG, Xi JY, et al. Decrease of CD4(+)CD25(high)Foxp3(+) regulatory T cells and elevation of CD19(+)BAFF-R(+) B cells and soluble ICAM-1 in myasthenia gravis. Clin Immunol 2008;126(2):180-8
  • Xu WH, Zhang AM, Ren MS, et al. Changes of Treg-associated molecules on CD4+CD25 +Treg cells in myasthenia gravis and effects of immunosuppressants. J Clin Immunol 2012;32(5):975-83
  • Luther C, Poeschel S, Varga M, et al. Decreased frequency of intrathymic regulatory T cells in patients with myasthenia-associated thymoma. J Neuroimmunol 2005;164(1-2):124-8
  • Zhang Y, Wang HB, Chi LJ, et al. The role of FoxP3+CD4+CD25hi Tregs in the pathogenesis of myasthenia gravis. Immunol Lett 2009;122(1):52-7
  • Zhang J, Chen Y, Jia G, et al. FOXP3 -3279 and IVS9+459 polymorphisms are associated with genetic susceptibility to myasthenia gravis. Neurosci Lett 2013;534:274-8
  • Laan M, Peterson P. The many faces of AIRE in central tolerance. Front Immunol 2013;4:326
  • Mathis D, Benoist C. Aire. Annu Rev Immunol 2009;27:287-312
  • Wolff AS, Oftedal BE, Kisand K, et al. Flow cytometry study of blood cell subtypes reflects autoimmune and inflammatory processes in autoimmune polyendocrine syndrome type I. Scand J Immunol 2010;71(6):459-67
  • Laakso SM, Laurinolli TT, Rossi LH, et al. Regulatory T cell defect in APECED patients is associated with loss of naive FOXP3(+) precursors and impaired activated population. J Autoimmun 2010;35(4):351-7
  • Aricha R, Feferman T, Scott HS, et al. The susceptibility of AIRE(-/-) mice to experimental myasthenia gravis involves alterations in regulatory T cells. J Autoimmun 2011;36(1):16-24
  • Nguyen TL, Sullivan NL, Ebel M, et al. Antigen-specific TGF-beta-induced regulatory T cells secrete chemokines, regulate T cell trafficking, and suppress ongoing autoimmunity. J Immunol 2011;187(4):1745-53
  • Lan Q, Fan H, Quesniaux V, et al. Induced Foxp3(+) regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases? J Mol Cell Biol 2012;4(1):22-8
  • Chatterjee S, Eby JM, Al-Khami AA, et al. A quantitative increase in regulatory T cells controls development of vitiligo. J Invest Dermatol 2014;134(5):1285-94
  • Chakraborty R, Mahendravada A, Perna SK, et al. Robust and cost effective expansion of human regulatory T cells highly functional in a xenograft model of graft-versus-host disease. Haematologica 2013;98(4):533-7
  • Putnam AL, Brusko TM, Lee MR, et al. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 2009;58(3):652-62
  • Gopisetty A, Bhattacharya P, Haddad C, et al. OX40L/Jagged1 cosignaling by GM-CSF-induced bone marrow-derived dendritic cells is required for the expansion of functional regulatory T cells. J Immunol 2013;190(11):5516-25
  • Ganesh BB, Cheatem DM, Sheng JR, et al. GM-CSF-induced CD11c+CD8a--dendritic cells facilitate Foxp3+ and IL-10+ regulatory T cell expansion resulting in suppression of autoimmune thyroiditis. Int Immunol 2009;21(3):269-82
  • Bhattacharya P, Gopisetty A, Ganesh BB, et al. GM-CSF-induced, bone-marrow-derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms. J Leukoc Biol 2011;89(2):235-49
  • Arellano M, Lonial S. Clinical uses of GM-CSF, a critical appraisal and update. Biologics 2008;2(1):13-27
  • Sheng JR, Li LC, Ganesh BB, et al. Regulatory T cells induced by GM-CSF suppress ongoing experimental myasthenia gravis. Clin Immunol 2008;128(2):172-80
  • Sheng JR, Muthusamy T, Prabhakar BS, et al. GM-CSF-induced regulatory T cells selectively inhibit anti-acetylcholine receptor-specific immune responses in experimental myasthenia gravis. J Neuroimmunol 2011;240-241:65-73
  • Rowin J, Thiruppathi M, Arhebamen E, et al. Granulocyte macrophage colony-stimulating factor treatment of a patient in myasthenic crisis: effects on regulatory T cells. Muscle Nerve 2012;46(3):449-53
  • Thiruppathi M, Rowin J, Li Jiang Q, et al. Functional defect in regulatory T cells in myasthenia gravis. Ann N Y Acad Sci 2012;1274:68-76
  • Sonderegger I, Iezzi G, Maier R, et al. GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J Exp Med 2008;205(10):2281-94
  • Schottelius A. The role of GM-CSF in multiple sclerosis. Drug Res (Stuttg) 2013;63(Suppl 1):S8
  • Burmester GR, Weinblatt ME, McInnes IB, et al. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis 2013;72(9):1445-52
  • Behrens F, Tak PP, Ostergaard M, et al. MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis 2014. [Epub ahead of print]
  • Takeuchi T, Tanaka Y, Close D, et al. Efficacy and safety of mavrilimumab in Japanese subjects with rheumatoid arthritis: findings from a Phase IIa study. Mod Rheumatol 2015;25(1):21-30
  • Bhattacharya P, Budnick I, Singh M, et al. Dual role of GM-CSF as a Pro-inflammatory and a regulatory cytokine: implications for immune therapy. J Interferon Cytokine Res 2015. [Epub ahead of print]
  • Abou-Raya A, Abou-Raya S, Helmii M. The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. J Rheumatol 2013;40(3):265-72
  • Askmark H, Haggard L, Nygren I, et al. Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study. Eur J Neurol 2012;19(12):1554-60
  • Gatenby P, Lucas R, Swaminathan A. Vitamin D deficiency and risk for rheumatic diseases: an update. Curr Opin Rheumatol 2013;25(2):184-91
  • Urry Z, Chambers ES, Xystrakis E, et al. The role of 1alpha,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+ CD4+ T cells. Eur J Immunol 2012;42(10):2697-708
  • Alahgholi-Hajibehzad M, Oflazer P, Aysal F, et al. Regulatory function of CD4(+)CD25(++) T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity. J Neuroimmunol 2015;281:51-60
  • Peluso I, Fantini MC, Fina D, et al. IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J Immunol 2007;178(2):732-9
  • Li Y, Rauniyar VK, Yin WF, et al. Serum IL-21 levels decrease with glucocorticoid treatment in myasthenia gravis. Neurol Sci 2014;35(1):29-34
  • Tuzun E, Meriggioli MN, Rowin J, et al. Myasthenia gravis patients with low plasma IL-6 and IFN-gamma benefit from etanercept treatment. J Autoimmun 2005;24(3):261-8
  • Fee DB, Kasarskis EJ. Myasthenia gravis associated with etanercept therapy. Muscle Nerve 2009;39(6):866-70
  • Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med 2011;365(22):2067-77
  • Nazzal D, Gradolatto A, Truffault F, et al. Human thymus medullary epithelial cells promote regulatory T-cell generation by stimulating interleukin-2 production via ICOS ligand. Cell Death Dis 2014;5:e1420
  • Utsugisawa K, Nagane Y, Obara D, et al. Interleukin-2 production by peripheral blood mononuclear cells from patients with myasthenia gravis. Eur Neurol 2003;49(3):160-3
  • Konieczna P, Groeger D, Ziegler M, et al. Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells. Gut 2012;61(3):354-66
  • Kwon HK, Lee CG, So JS, et al. Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci USA 2010;107(5):2159-64
  • Kim HJ, Kim YJ, Lee SH, et al. Effects of Lactobacillus rhamnosus on allergic march model by suppressing Th2, Th17, and TSLP responses via CD4(+)CD25(+)Foxp3(+) Tregs. Clin Immunol 2014;153(1):178-86
  • Lavasani S, Dzhambazov B, Nouri M, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One 2010;5(2):e9009
  • O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 2005;128(3):541-51
  • Hwang I, Ahn G, Park E, et al. An acidic polysaccharide of Panax ginseng ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells. Immunol Lett 2011;138(2):169-78
  • Oliveira L, Correia A, Cristina Costa A, et al. Deficits in endogenous adenosine formation by ecto-5’-nucleotidase/CD73 impair neuromuscular transmission and immune competence in experimental autoimmune myasthenia gravis. Mediators Inflamm 2015;2015:460610
  • Zarek PE, Huang CT, Lutz ER, et al. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 2008;111(1):251-9
  • Ramlackhansingh AF, Bose SK, Ahmed I, et al. Adenosine 2A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease. Neurology 2011;76(21):1811-16
  • Mills JH, Thompson LF, Mueller C, et al. CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2008;105(27):9325-30
  • Niemela J, Ifergan I, Yegutkin GG, et al. IFN-beta regulates CD73 and adenosine expression at the blood-brain barrier. Eur J Immunol 2008;38(10):2718-26
  • Li N, Mu L, Wang J, et al. Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity. Eur J Immunol 2012;42(5):1140-51
  • Ju JH, Heo YJ, Cho ML, et al. Modulation of STAT-3 in rheumatoid synovial T cells suppresses Th17 differentiation and increases the proportion of Treg cells. Arthritis Rheum 2012;64(11):3543-52
  • Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 2014;13(6):668-77
  • Ludwig-Portugall I, Hamilton-Williams EE, Gotot J, et al. CD25+ T(reg) specifically suppress auto-Ab generation against pancreatic tissue autoantigens. Eur J Immunol 2009;39(1):225-33

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.