Journal of Neuroimmunology
Volume 215, Issue 1 , Pages 90-95 , 30 October 2009

Expression of TH1 and TH17 cytokines and transcription factors in multiple sclerosis patients: Does baseline T-Bet mRNA predict the response to interferon-beta treatment?

  • Jelena Drulovic

      Affiliations

    • Institute of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 6, 11000 Belgrade, Serbia
    • Corresponding Author InformationCorresponding author. Tel./fax: +381 11 2685 662.
  • ,
  • Emina Savic

      Affiliations

    • Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
  • ,
  • Tatjana Pekmezovic

      Affiliations

    • Institute of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 6, 11000 Belgrade, Serbia
  • ,
  • Sarlota Mesaros

      Affiliations

    • Institute of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 6, 11000 Belgrade, Serbia
  • ,
  • Nebojsa Stojsavljevic

      Affiliations

    • Institute of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 6, 11000 Belgrade, Serbia
  • ,
  • Irena Dujmovic-Basuroski

      Affiliations

    • Institute of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 6, 11000 Belgrade, Serbia
  • ,
  • Jelena Kostic

      Affiliations

    • Institute of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 6, 11000 Belgrade, Serbia
  • ,
  • Vladimir Vasic

      Affiliations

    • Department of Mathematics and Statistics, Faculty of Economics, University of Belgrade, Kamenicka 6, 11000 Belgrade, Serbia
  • ,
  • Marija Mostarica Stojkovic

      Affiliations

    • Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
  • ,
  • Dusan Popadic

      Affiliations

    • Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia

Received 26 March 2009 ,Revised 15 July 2009 ,Accepted 21 July 2009.

References 

  1. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, et al. Phenotypic and functional features of human Th17 cells. J. Exp. Med. 2007;204:1849–1861
  2. Becher B, Giacomini PS, Pelletier D, McCrea E, Prat A, Antel JP. Interferon-gamma secretion by peripheral blood T-cell subsets in multiple sclerosis: correlation with disease phase and interferon-beta therapy. Ann. Neurol. 1999;45:247–250
  3. Beck J, Rondot P, Catinot L, Falcoff E, Kirchner H, Wietzerbin J. Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: do cytokines trigger off exacerbations?. Acta Neurol. Scand. 1988;78:318–323
  4. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J. Exp. Med. 2004;200:79–87
  5. Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat. Immunol. 2007;8:345–350
  6. Comabella M, Rio J, Espejo C, Ruiz de Villa M, Al-Zayat H, Nos C, et al. Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis. Clin. Immunol. 2009;130:145–150
  7. Dayal AS, Jensen MA, Lledo A, Arnason BG. Interferon-gamma-secreting cells in multiple sclerosis patients treated with interferon beta-1b. Neurology. 1995;45:2173–2177
  8. Frisullo G, Angelucci F, Caggiula M, Nociti V, Iorio R, Patanella AK, et al. pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity. J. Neurosci. Res. 2006;84:1027–1036
  9. Gocke AR, Cravens PD, Ben LH, Hussain RZ, Northrop SC, Racke MK, et al. T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J. Immunol. 2007;178:1341–1348
  10. Graber JJ, Allie SR, Mullen KM, Jones MV, Wang T, Krishnan C, et al. Interleukin-17 in transverse myelitis and multiple sclerosis. J. Neuroimmunol. 2008;196:124–132
  11. Harrington LE, Mangan PR, Weaver CT. Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr. Opin. Immunol. 2006;18:349–356
  12. Hedegaard CJ, Krakauer M, Bendtzen K, Sorensen PS, Sellebjerg F, Nielsen CH. The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis. Clin. Immunol. 2008;129:80–89
  13. Hedegaard CJ, Krakauer M, Bendtzen K, Lund H, Sellebjerg F, Nielsen CH. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology. 2008;125:161–169
  14. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–1133
  15. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, et al. Human TH17 lymphocytes promote blood–brain barrier disruption and central nervous system inflammation. Nat. Med. 2007;13:1173–1175
  16. Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J. Immunol. 2006;177:566–573
  17. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–1452
  18. Lee YK, Turner H, Maynard CL, Oliver JR, Chen D, Elson CO, et al. Late developmental plasticity in the T helper 17 lineage. Immunity. 2009;30:92–107
  19. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 2002;8:500–508
  20. Lord GM, Rao RM, Choe H, Sullivan BM, Lichtman AH, Luscinskas FW, et al. T-bet is required for optimal proinflammatory CD4+ T-cell trafficking. Blood. 2005;106:3432–3439
  21. Lovett-Racke AE, Rocchini AE, Choy J, Northrop SC, Hussain RZ, Ratts RB, et al. Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity. 2004;21:719–731
  22. Martin-Saavedra FM, Flores N, Dorado B, Eguiluz C, Bravo B, Garcia-Merino A, et al. Beta-interferon unbalances the peripheral T cell proinflammatory response in experimental autoimmune encephalomyelitis. Mol. Immunol. 2007;44:3597–3607
  23. Matsuda JL, George TC, Hagman J, Gapin L. Temporal dissection of T-bet functions. J. Immunol. 2007;178(6):3457–3465
  24. Matusevicius D, Kivisakk P, He B, Kostulas N, Ozenci V, Fredrikson S, et al. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult. Scler. 1999;5:101–104
  25. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. 2001;50:121–127
  26. Nicoletti F, Di Marco R, Patti F, Zaccone P, L'Episcopo MR, Reggio E, et al. Short-term treatment of relapsing remitting multiple sclerosis patients with interferon (IFN)-beta1B transiently increases the blood levels of interleukin (IL)-6, IL-10 and IFN-gamma without significantly modifying those of IL-1beta, IL-2, IL-4 and tumour necrosis factor-alpha. Cytokine. 2000;12:682–687
  27. Noronha A, Toscas A, Jensen MA. Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J. Neuroimmunol. 1993;46:145–153
  28. Panitch HS, Hirsch RL, Haley AS, Johnson KP. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet. 1987;1:893–895
  29. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 2005;6:1133–1141
  30. Petereit HF, Nolden S, Schoppe S, Bamborschke S, Pukrop R, Heiss WD. Low interferon gamma producers are better treatment responders: a two-year follow-up of interferon beta-treated multiple sclerosis patients. Mult. Scler. 2002;8:492–494
  31. PRISMS . (Prevention of relapses and disability by interferon beta-1a subcutaneously in multiple sclerosis) Study Group. Randomized double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet. 1998;352:1498–1504
  32. Rio J, Nos C, Tintore M, Borras C, Galan I, Comabella M, et al. Assessment of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta: implications for clinical trials. Ann. Neurol. 2002;52:400–406
  33. Rio J, Nos C, Tintore M, Tellez N, Galan I, Pelayo R, et al. Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients. Ann. Neurol. 2006;59:344–352
  34. Romagnani, S., Maggi, E., Liotta, F., Cosmi, L., Annunziato, F., in press. Properties and origin of human Th17 cells. Mol. Immunol. doi:10.1016/j.molimm.2008.12.019.
  35. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 2005;23:683–747
  36. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. Novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655–669
  37. Szabo SJ, Sullivan BM, Peng SL, Glimcher LH. Molecular mechanisms regulating Th1 immune responses. Annu. Rev. Immunol. 2003;21:713–758
  38. The IFNB Multiple Sclerosis Study Group . Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology. 1993;43:655–661
  39. Trojano M, Avolio C, Liuzzi GM, Ruggieri M, Defazio G, Liguori M, et al. Changes of serum sICAM-1 and MMP-9 induced by rIFNbeta-1b treatment in relapsing-remitting MS. Neurology. 1999;53:1402–1408
  40. Underhill GH, Zisoulis DG, Kolli KP, Ellies LG, Marth JD, Kansas GS. A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells. Blood. 2005;106:3867–3873
  41. van Boxel-Dezaire AH, van Trigt-Hoff SC, Killestein J, Schrijver HM, van Houwelingen JC, Polman CH, et al. Contrasting responses to interferon beta-1b treatment in relapsing-remitting multiple sclerosis: does baseline interleukin-12p35 messenger RNA predict the efficacy of treatment?. Ann. Neurol. 2000;48:313–322
  42. Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol. 2007;25:821–852
  43. Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, et al. Global mapping of H3 K4me3 and H3 K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity. 2009;30:155–167
  44. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol. 1990;8:579–621

PII: S0165-5728(09)00292-6

doi: 10.1016/j.jneuroim.2009.07.010

Journal of Neuroimmunology
Volume 215, Issue 1 , Pages 90-95 , 30 October 2009