Modeling the effector - Regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

BMC Systems Biology

Volumn 5, Issue , 2011, Pages

  Vélez de Mendizábal, Nieves ^a,b   Carneiro, Jorge ^c   Solé, Ricard V ^d   Goñi, Joaquín ^a   Bragard, Jean ^a   Martinez Forero, Ivan ^a   Martinez Pasamar, Sara ^e   Sepulcre, Jorge ^a   Torrealdea, Javier ^b   Bagnato, Francesca ^f   Garcia Ojalvo, Jordi ^g   Villoslada, Pablo ^e  

^a UNIVERSITY OF NAVARRA   (Spain)

^b UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^c INSTITUTO GULBENKIAN DE CIÊNCIA   (Portugal)

^d UNIVERSITAT POMPEU FABRA   (Spain)

^e HOSPITAL CLÍNIC   (Spain)

^f NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^g UNIVERSITAT POLITÈCNICA DE CATALUNYA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; BIOLOGICAL MODEL; COMPUTER SIMULATION; FEEDBACK SYSTEM; HUMAN; IMMUNOLOGY; IMMUNOTHERAPY; LYMPHOCYTE ACTIVATION; METHODOLOGY; MULTIPLE SCLEROSIS; PATHOLOGY; SYSTEMS BIOLOGY; T LYMPHOCYTE SUBPOPULATION;

COMPUTER SIMULATION; FEEDBACK, PHYSIOLOGICAL; HUMANS; IMMUNOTHERAPY; LYMPHOCYTE ACTIVATION; MODELS, BIOLOGICAL; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; SYSTEMS BIOLOGY; T-LYMPHOCYTE SUBSETS;

EID: 79960554264     PISSN: None     EISSN: 17520509     Source Type: Journal    
DOI: 10.1186/1752-0509-5-114     Document Type: Article

References (61)

1. Compston A, Coles A. Multiple sclerosis. Lancet 2008, 372(9648):1502-1517. 10.1016/S0140-6736(08)61620-7, 18970977.
2. Vollmer T. The natural history of relapses in multiple sclerosis. J Neurol Sci 2007, 256(Suppl 1):S5-13.
3. Stone LA, Frank JA, Albert PS, Bash C, Smith ME, Maloni H, McFarland HF. The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann Neurol 1995, 37(5):611-619. 10.1002/ana.410370511, 7755356.
4. Chiu AW, Richert N, Ehrmantraut M, Ohayon J, Gupta S, Bomboi G, Gaindh D, Cantor FK, Frank JA, McFarland HF, et al. Heterogeneity in Response to Interferon Beta in Patients With Multiple Sclerosis. Arch Neurol 2009, 66(1):e1-5.
5. Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D. Early onset multiple sclerosis: a longitudinal study. Neurology 2002, 59(7):1006-1010.
6. Steinman L. Multiple sclerosis: a two-stage disease. Nat Immunol 2001, 2(9):762-764. 10.1038/ni0901-762, 11526378.
7. Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000, 343(20):1430-1438. 10.1056/NEJM200011163432001, 11078767.
8. Buljevac D, Flach HZ, Hop WC, Hijdra D, Laman JD, Savelkoul HF, Der Meche FG, van Doorn PA, Hintzen RQ. Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain 2002, 125(Pt 5):952-960.
9. Buljevac D, Hop WC, Reedeker W, Janssens AC, van der Meche FG, van Doorn PA, Hintzen RQ. Self reported stressful life events and exacerbations in multiple sclerosis: prospective study. BMJ 2003, 327(7416):646. 10.1136/bmj.327.7416.646, 196389, 14500435.
10. Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. AnnuRevImmunol 1992, 10:153-187.
11. Hauser SL, Oksenberg JR. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 2006, 52(1):61-76. 10.1016/j.neuron.2006.09.011, 17015227.
12. Diaz-Villoslada P, Shih A, Shao L, Genain CP, Hauser SL. Autoreactivity to myelin antigens: myelin/oligodendrocyte glycoprotein is a prevalent autoantigen. JNeuroimmunol 1999, 99(1):36-43.
13. Villoslada P, Abel K, Heald N, Goertsches R, Hauser SL, Genain CP. Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin oligodendrocyte glycoprotein in naive outbred primates. Eur J Immunol 2001, 31(10):2942-2950. 10.1002/1521-4141(2001010)31:10<2942::AID-IMMU2942>3.0.CO;2-M, 11592070.
14. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995, 155(3):1151-1164.
15. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 2001, 182:18-32. 10.1034/j.1600-065X.2001.1820102.x, 11722621.
16. Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998, 188(2):287-296. 10.1084/jem.188.2.287, 2212461, 9670041.
17. Thornton AM, Shevach EM. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol 2000, 164(1):183-190.
18. Shevach EM, McHugh RS, Piccirillo CA, Thornton AM. Control of T-cell activation by CD4+ CD25+ suppressor T cells. Immunol Rev 2001, 182:58-67. 10.1034/j.1600-065X.2001.1820104.x, 11722623.
19. Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 2006, 212:8-27. 10.1111/j.0105-2896.2006.00427.x, 16903903.
20. Fontenot JD, Rudensky AY. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 2005, 6(4):331-337. 10.1038/ni1179, 15785758.
21. van der Vliet HJ, Nieuwenhuis EE. IPEX as a result of mutations in FOXP3. Clin Dev Immunol 2007, 2007:89017. 2248278, 18317533.
22. Ochs HD, Gambineri E, Torgerson TR. IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity. Immunol Res 2007, 38(1-3):112-121. 10.1007/s12026-007-0022-2, 17917016.
23. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. JExpMed 2004, 199(7):971-979.
24. Martinez-Forero I, Garcia-Munoz R, Martinez-Pasamar S, Inoges S, Lopez-Diaz de Cerio A, Palacios R, Sepulcre J, Moreno B, Gonzalez Z, Fernandez-Diez B, et al. IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. Eur J Immunol 2008, 38(2):576-586. 10.1002/eji.200737271, 18200504.
25. Kukreja A, Cost G, Marker J, Zhang C, Sun Z, Lin-Su K, Ten S, Sanz M, Exley M, Wilson B, et al. Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest 2002, 109(1):131-140. 150819, 11781358.
26. Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 2003, 100(14):8372-8377. 10.1073/pnas.1533209100, 166236, 12826605.
27. Almeida AR, Zaragoza B, Freitas AA. Indexation as a novel mechanism of lymphocyte homeostasis: the number of CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cells. J Immunol 2006, 177(1):192-200.
28. Lund JM, Hsing L, Pham TT, Rudensky AY. Coordination of early protective immunity to viral infection by regulatory T cells. Science 2008, 320(5880):1220-1224. 10.1126/science.1155209, 2519146, 18436744.
29. Carneiro J, Leon K, Caramalho I, van den Dool C, Gardner R, Oliveira V, Bergman ML, Sepulveda N, Paixao T, Faro J, et al. When three is not a crowd: a Crossregulation Model of the dynamics and repertoire selection of regulatory CD4(+) T cells. Immunol Rev 2007, 216:48-68.
30. Germain RN. The art of the probable: system control in the adaptive immune system. Science 2001, 293(5528):240-245. 10.1126/science.1062946, 11452112.
31. Kekalainen E, Tuovinen H, Joensuu J, Gylling M, Franssila R, Pontynen N, Talvensaari K, Perheentupa J, Miettinen A, Arstila TP. A defect of regulatory T cells in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Immunol 2007, 178(2):1208-1215.
32. Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat Immunol 2005, 6(4):353-360.
33. O'Connor W, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, Kolls JK, Flavell RA. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 2009, 10(6):603-609. 10.1038/ni.1736, 2709990, 19448631.
34. Mackey MC, Milton JG. Dynamical diseases. Ann N Y Acad Sci 1987, 504:16-32. 10.1111/j.1749-6632.1987.tb48723.x, 3477113.
35. Villoslada P, Steinman L, Baranzini SE. Systems biology and its application to the understanding of neurological diseases. Ann Neurol 2009, 65(2):124-139. 10.1002/ana.21634, 19260029.
36. von Herrath MG, Sanda S, Herold K. Type 1 diabetes as a relapsing-remitting disease?. Nat Rev Immunol 2007, 7:988-994. 10.1038/nri2192, 17982429.
37. Goodnow CC, Sprent J, Fazekas de St Groth B, Vinuesa CG. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 2005, 435(7042):590-597. 10.1038/nature03724, 15931211.
38. Leon K, Faro J, Lage A, Carneiro J. Inverse correlation between the incidences of autoimmune disease and infection predicted by a model of T cell mediated tolerance. J Autoimmun 2004, 22(1):31-42. 10.1016/j.jaut.2003.10.002, 14709411.
39. Lafaille JJ, Nagashima K, Katsuki M, Tonegawa S. High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice. Cell 1994, 78(3):399-408. 10.1016/0092-8674(94)90419-7, 7520367.
40. Burroughs NJ, Miguel Paz Mendes de Oliveira B, Adrego Pinto A. Regulatory T cell adjustment of quorum growth thresholds and the control of local immune responses. J Theor Biol 2006, 241(1):134-141. 10.1016/j.jtbi.2005.11.010, 16403532.
41. Wu Y, Zhu WQ. Stochastic analysis of a pulse-type prey-predator model. Phys Rev E Stat Nonlin Soft Matter Phys 2008, 77(4 Pt 1):041911.
42. Borghans JA, De Boer RJ, Sercarz E, Kumar V. T cell vaccination in experimental autoimmune encephalomyelitis: a mathematical model. J Immunol 1998, 161(3):1087-1093.
43. Borghans JA, De Boer RJ. A minimal model for T-cell vaccination. Proc Biol Sci 1995, 259(1355):173-178. 10.1098/rspb.1995.0025, 7732037.
44. Kitano H. A robustness-based approach to systems-oriented drug design. Nat Rev Drug Discov 2007, 6(3):202-210. 10.1038/nrd2195, 17318209.
45. Palacios R, Goni J, Martinez-Forero I, Iranzo J, Sepulcre J, Melero I, Villoslada P. A network analysis of the human T-cell activation gene network identifies JAGGED1 as a therapeutic target for autoimmune diseases. PLoS ONE 2007, 2(11):e1222. 10.1371/journal.pone.0001222, 2077806, 18030350.
46. Carlson JM, Doyle J. Complexity and robustness. Proc Natl Acad Sci USA 2002, 99(Suppl 1):2538-2545. 128573, 11875207.
47. Wucherpfennig KW. Mechanisms for the induction of autoimmunity by infectious agents. J Clin Invest 2001, 108(8):1097-1104. 209539, 11602615.
48. Oksenberg JR, Baranzini SE, Sawcer S, Hauser SL. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nat Rev Genet 2008, 9(7):516-526. 10.1038/nrg2395, 18542080.
49. Bagnato F, Jeffries N, Richert ND, Stone RD, Ohayon JM, McFarland HF, Frank JA. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain 2003, 126(Pt 8):1782-1789.
50. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol 2007, 8(12):1353-1362. 10.1038/ni1536, 17982458.
51. Lawrence CW, Ream RM, Braciale TJ. Frequency, specificity, and sites of expansion of CD8+ T cells during primary pulmonary influenza virus infection. J Immunol 2005, 174(9):5332-5340.
52. Zhang X, Koldzic DN, Izikson L, Reddy J, Nazareno RF, Sakaguchi S, Kuchroo VK, Weiner HL. IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells. Int Immunol 2004, 16(2):249-256. 10.1093/intimm/dxh029, 14734610.
53. Walker J, Rigley K. Gene expression profiling in human peripheral blood mononuclear cells using high-density filter-based cDNA microarrays. J Immunol Methods 2000, 239(1-2):167-179. 10.1016/S0022-1759(00)00181-2, 10821957.
54. Walker LS, Chodos A, Eggena M, Dooms H, Abbas AK. Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo. J Exp Med 2003, 198(2):249-258. 10.1084/jem.20030315, 2194065, 12874258.
55. Maloy KJ, Powrie F. Regulatory T cells in the control of immune pathology. Nat Immunol 2001, 2(9):816-822. 10.1038/ni0901-816, 11526392.
56. Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med 2005, 201(5):723-735. 10.1084/jem.20041982, 2212841, 15753206.
57. Shaw AS. How T cells 'find' the right dendritic cell. Nat Immunol 2008, 9(3):229-230. 10.1038/ni0308-229, 18285771.
58. Abta R, Shnerb NM. Angular velocity variations and stability of spatially explicit prey-predator systems. Phys Rev E Stat Nonlin Soft Matter Phys 2007, 75(5 Pt 1):051914.
59. Reichenbach T, Mobilia M, Frey E. Coexistence versus extinction in the stochastic cyclic Lotka-Volterra model. Phys Rev E Stat Nonlin Soft Matter Phys 2006, 74(5 Pt 1):051907.
60. Rozenfeld AF, Albano EV. Critical and oscillatory behavior of a system of smart preys and predators. Phys Rev E Stat Nonlin Soft Matter Phys 2001, 63(6 Pt 1):061907.
61. Kyewski B, Klein L. A central role for central tolerance. Annu Rev Immunol 2006, 24:571-606. 10.1146/annurev.immunol.23.021704.115601, 16551260.