The essential role of T cells in multiple sclerosis: A reappraisal

Biomedical Journal

Volumn 37, Issue 2, 2014, Pages 34-40

  Constantinescu, Cris S ^a   Gran, Bruno ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

Experimental autoimmune encephalomyelitis; Hookworm; Multiple sclerosis; Th1 Treg; Th17; Treatment

Indexed keywords

CD4 ANTIGEN; GAMMA INTERFERON; IMMUNOMODULATING AGENT; IMMUNOSUPPRESSIVE AGENT;

ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DISEASE ACTIVITY; DISEASE COURSE; DISEASE PREDISPOSITION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNOPATHOGENESIS; IMMUNOREGULATION; MULTIPLE SCLEROSIS; NONHUMAN; REGULATORY T LYMPHOCYTE; RELAPSE; T LYMPHOCYTE; TARGET CELL; TH1 CELL; TH17 CELL; TH2 CELL; ANIMAL; CENTRAL NERVOUS SYSTEM; CYTOLOGY; IMMUNITY; IMMUNOLOGY; IMMUNOTHERAPY;

ANIMALS; B-LYMPHOCYTES; CENTRAL NERVOUS SYSTEM; HUMANS; IMMUNE SYSTEM PROCESSES; IMMUNOTHERAPY; MULTIPLE SCLEROSIS; T-LYMPHOCYTES;

EID: 84899015008     PISSN: 23194170     EISSN: None     Source Type: Journal    
DOI: 10.4103/2319-4170.128746     Document Type: Article

References (71)

1. Compston A, Coles A. Multiple sclerosis. Lancet 2008;372:1502-17.
2. Popescu BF, Pirko I, Lucchinetti CF. Pathology of multiple sclerosis: Where do we stand? Continuum 2013;19:901-21.
3. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 2011;164:1079-106.
4. Constantinescu CS, Hilliard B, Fujioka T, Bhopale MK, Calida D, Rostami AM. Pathogenesis of neuroimmunologic diseases. Experimental models. Immunol Res 1998;17:217-27.
5. t Hart BA, Gran B, Weissert R. EAE: Imperfect but useful models of multiple sclerosis. Trends Mol Med 2011;17:119-25.
6. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992;356:63-6.
7. Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354:899-910.
8. Odoardi F, Sie C, Streyl K, Ulaganathan VK, Schlager C, Lodygin D, et al. T cells become licensed in the lung to enter the central nervous system. Nature 2012;488:675-9.
9. Yokote H, Miyake S, Croxford JL, Oki S, Mizusawa H, Yamamura T. NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora. Am J Pathol 2008;173:1714-23.
10. Ochoa-Reparaz J, Mielcarz DW, Ditrio LE, Burroughs AR, Foureau DM, Haque-Begum S, et al. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol 2009;183:6041-50.
11. Zamvil S, Nelson P, Trotter J, Mitchell D, Knobler R, Fritz R, et al. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 1985;317:355-8.
12. Urban JL, Kumar V, Kono DH, Gomez C, Horvath SJ, Clayton J, et al. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 1988;54:577-92.
13. Uccelli A, Giunti D, Salvetti M, Ristori G, Fenoglio D, Abbruzzese, et al. A restricted T cell response to myelin basic protein (MBP) is stable in multiple sclerosis (MS) patients. Clin Exp Immunol 1998;111:186-92.
14. Clark L, Heber-Katz E, Rostami A. Shared T-cell receptor gene usage in experimental allergic neuritis and encephalomyelitis. Ann Neurol 1992;31:587-92.
15. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348-57.
16. Voskuhl RR, Martin R, Bergman C, Dalal M, Ruddle NH, McFarland HF. T helper 1 (Th1) functional phenotype of human myelin basic protein-specific T lymphocytes. Autoimmunity 1993;15:137-43.
17. Constantinescu CS, Hilliard B, Ventura E, Wysocka M, Showe L, Lavi E, et al. Modulation of susceptibility and resistance to an autoimmune model of multiple sclerosis in prototypically susceptible and resistant strains by neutralization of interleukin-12 and interleukin-4, respectively. Clin Immunol 2001;98:23-30.
18. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421:744-8.
19. Touil T, Fitzgerald D, Zhang GX, Rostami AM, Gran B. Pathophysiology of interleukin-23 in experimental autoimmune encephalomyelitis. Drug News Perspect 2006;19:77-83.
20. Gran B, Zhang GX, Yu S, Li J, Chen XH, Ventura ES, et al. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: Evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J Immunol 2002;169:7104-10.
21. Zhang GX, Gran B, Yu S, Li J, Siglienti I, Chen X, et al. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 2003;170:2153-60.
22. Zhang GX, Yu S, Gran B, Li J, Siglienti I, Chen X, et al. Role of IL-12 receptor beta 1 in regulation of T cell response by APC in experimental autoimmune encephalomyelitis. J Immunol 2003;171:4485-92.
23. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005;201:233-40.
24. Nyirenda MH, O'Brien K, Sanvito L, Constantinescu CS, Gran B. Modulation of regulatory T cells in health and disease: Role of toll-like receptors. Inflamm Allergy Drug Targets 2009;8:124-9.
25. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+regulatory T cells in patients with multiple sclerosis. J Exp Med 2004;199:971-9.
26. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006;441:235-8.
27. Nyirenda MH, Sanvito L, Darlington PJ, O'Brien K, Zhang GX, Constantinescu CS, et al. TLR2 stimulation drives human naive and effector regulatory T cells into a Th17-like phenotype with reduced suppressive function. J Immunol 2011;187:2278-90.
28. Edwards LJ, Robins RA, Constantinescu CS. Th17/Th1 phenotype in demyelinating disease. Cytokine 2010;50:19-23.
29. Kebir H, Ifergan I, Alvarez JI, Bernard M, Poirier J, Arbour N, et al. Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis. Ann Neurol 2009;66:390-402.
30. Vollmer TL, Wynn DR, Alam MS, Valdes J. A phase 2, 24-week, randomized, placebo-controlled, double-blind study examining the efficacy and safety of an anti-interleukin-12 and -23 monoclonal antibody in patients with relapsing-remitting or secondary progressive multiple sclerosis. Mult Scler 2011;17:181-91.
31. Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH, et al. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: A phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008;7:796-804.
32. Longbrake EE, Racke MK. Why did IL-12/IL-23 antibody therapy fail in multiple sclerosis? Expert Rev Neurother 2009;9:319-21.
33. Constantinescu CS, Wysocka M, Hilliard B, Ventura ES, Lavi E, Trinchieri G, et al. Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis. J Immunol 1998;161:5097-104.
34. Constantinescu CS, Hilliard B, Wysocka M, Ventura ES, Bhopale MK, Trinchieri G, et al. IL-12 reverses the suppressive effect of the CD40 ligand blockade on experimental autoimmune encephalomyelitis (EAE). J Neurol Sci 1999;171:60-4.
35. Gran B, Chu N, Zhang GX, Yu S, Li Y, Chen XH, et al. Early administration of IL-12 suppresses EAE through induction of interferon-gamma. J Immunol 2004;156:123-31.
36. Axtell RC, de Jong BA, Boniface K, van der Voort LF, Bhat R, De Sarno P, et al. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat Med 2010;16:406-12.
37. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, et al. The encephalitogenicity of T (H) 17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nature immunology 2011;12:568-75.
38. Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011;12:560-7.
39. Panitch HS, Hirsch RL, Haley AS, Johnson KP. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1987;1:893-5.
40. Jagessar SA, Gran B, Heijmans N, Bauer J, Laman JD, t Hart BA, et al. Discrepant effects of human interferon-gamma on clinical and immunological disease parameters in a novel marmoset model for multiple sclerosis. J Neuroimmune Pharmacol 2012;7:253-65.
41. Sanvito L, Constantinescu CS, Gran B. The multifaceted role of interferon-gamma in central nervous system autoimmune demyelination. Open Autoimmun J 2010;2:151-9.
42. Lehtimaki S, Lahesmaa R. Regulatory T cells control immune responses through their non-redundant tissue specific features. Front Immunol 2013;4:294.
43. Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, et al. Functional delineation and differentiation dynamics of human CD4+T cells expressing the FoxP3 transcription factor. Immunity 2009;30:899-911.
44. Miyara M, Gorochov G, Ehrenstein M, Musset L, Sakaguchi S, Amoura Z. Human FoxP3+regulatory T cells in systemic autoimmune diseases. Autoimmun Rev 2011;10:744-55.
45. Miyara M, Sakaguchi S. Human FoxP3(+) CD4(+) regulatory T cells: Their knowns and unknowns. Immunol Cell Biol 2011;89:346-51.
46. Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, et al . The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 2008;453:106-9.
47. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006;24:179-89.
48. Trinschek B, Lussi F, Haas J, Wildemann B, Zipp F, Wiendl H, et al. Kinetics of IL-6 production defines T effector cell responsiveness to regulatory T cells in multiple sclerosis. PloS One 2013;8:e77634.
49. Dominguez-Villar M, Baecher-Allan CM, Hafler DA. Identification of T helper type 1-like, Foxp3+regulatory T cells in human autoimmune disease. Nat Med 2011;17:673-5.
50. Schneider A, Long SA, Cerosaletti K, Ni CT, Samuels P, Kita M, et al. In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive T (regs) involves IL-6-mediated signaling. Sci Transl Med 2013;5:170ra15.
51. Braitch M, Harikrishnan S, Robins RA, Nichols C, Fahey AJ, Showe L, et al. Glucocorticoids increase CD4CD25 cell percentage and Foxp3 expression in patients with multiple sclerosis. Acta Neurol Scand 2009;119:239-45.
52. Friese MA, Fugger L. Autoreactive CD8+T cells in multiple sclerosis: A new target for therapy? Brain 2005;128:1747-63.
53. Chanvillard C, Jacolik RF, Infante-Duarte C, Nayak RC. The role of natural killer cells in multiple sclerosis and their therapeutic implications. Front Immunol 2013;4:63.
54. Jager A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 2009;183:7169-77.
55. Xu W, Li R, Dai Y, Wu A, Wang H, Cheng C, et al. IL-22 secreting CD4+T cells in the patients with neuromyelitis optica and multiple sclerosis. J Neuroimmunol 2013;261:87-91.
56. Das Sarma J. T cells and IL-17/IL-17R signaling axis in CNS inflammation. Int J Interf Cytok Mediat Res 2010;2:149-55.
57. International Multiple Sclerosis Genetics C, Wellcome Trust Case Control C, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476:214-9.
58. Disanto G, Kjetil Sandve G, Ricigliano VA, Pakpoor J, Berlanga-Taylor AJ, Handel AE, et al. DNase hypersensitive sites and association with multiple sclerosis. Hum Mol Genet 2014;23:942-8.
59. Lim SY, Constantinescu CS. Current and future disease-modifying therapies in multiple sclerosis. Int J Clin Pract 2010;64:637-50.
60. Burt RK, Cohen B, Rose J, Petersen F, Oyama Y, Stefoski D, et al. Hematopoietic stem cell transplantation for multiple sclerosis. Arch Neurol 2005;62:860-4.
61. Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ, Cassiani-Ingoni R, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med 2005;201:805-16.
62. Abrahamsson SV, Angelini DF, Dubinsky AN, Morel E, Oh U, Jones JL, et al. Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis. Brain 2013;136:2888-903.
63. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292-302.
64. Corvol JC, Pelletier D, Henry RG, Caillier SJ, Wang J, Pappas D, et al. Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event. Proc Natl Acad Sci U S A 2008;105:11839-44.
65. Schulze-Topphoff U, Casazza S, Varrin-Doyer M, Pekarek K, Sobel RA, Hauser SL, et al. Tob1 plays a critical role in the activation of encephalitogenic T cells in CNS autoimmunity. J Exp Med 2013;210:1301-9.
66. Linington C, Bradl M, Lassmann H, Brunner C, Vass K. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 1988;130:443-54.
67. Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008;358:676-88.
68. Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 2009;132:1175-89.
69. Weiner HL. A shift from adaptive to innate immunity: A potential mechanism of disease progression in multiple sclerosis. J Neurol 2008;255 Suppl 1:3-11.
70. Romme Christensen J, Bornsen L, Ratzer R, Piehl F, Khademi M, Olsson T, et al. Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression. PloS One 2013;8:e57820.
71. Yamamura T, Gran B. Multiple Sclerosis Immunology. A Foundation for Current and Future Treatments. New York: Springer; 2013.