Autoimmune T cells play a key role as regulators and effectors of organ-specific autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components produce a plethora of inflammatory cytokines and mediators that contribute to myelin damage. The production of proinflammatory and regulatory cytokines by peripheral blood cells from patients with active and stable MS and healthy controls were examined. The results show that TNFa production was somewhat elevated in active MS with no significant increase in the level IFNg, whereas in the chronic phase the anti-inflammatory cytokines IL-10 and TGFb increased, accompanied by a reduction in IFNg when stimulated by myelin basic protein.
Waksman B. (1985) Mechanisms in multiple sclerosis . Nature318: 104-105 .
2.
Ota Ket al. (1990) T cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis . Nature346: 183-187 .
3.
Sharief MK , Hentges R. (1991) Association between tumor necrosis factor a and disease progression in patients with Multiple sclerosis . N Engl J Med325: 467-472 .
4.
Hartung HPet al. (1995) Circulating adhesion molecules and tumor necrosis factor in multiple sclerosis: correlation with magnetic resonance imaging . Ann Neurol38: 186-193 .
5.
Choffon M , Jillard C , Gauthier C , Grau G. (1992) Tumor necrosis factor production as possible predictor of relapse in patients with multiple sclerosis . Eur Cytokine Netw433: 523-531 .
6.
Panitch HS , Hirsch RL , Schindler J , Jonhnson KP. (1987) Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system . Neurology37: 1097-1102 .
7.
Navikas V , Link H. (1996) Review. Cytokines and the pathogenesis of multiple sclerosis . J Neurosc Res45: 322-333 .
8.
Rieckmann Pet al. (1994) Tumor necrosis factor a messenger RNA expression in patients with relapsingremitting multiple sclerosis is associated with disease activity . Ann Neurol37: 227-257 .
9.
Van der Veen RC , Stohlman SA. (1993) Encephalitogenic Th1 cells are inhibited by Th2 cells with related peptides specificity: relative roles of IL-4 and IL-10 . JNeuroimmunol48: 213-220 .
10.
Schluesener HJ , Lider O. (1989) Transforming growth factor b1and b2 cytokines with identical immunosuppressive effects and a potential role in the regulation of autoimmune T cell function . J Neuroimmunol24: 249-258 .
11.
De Waals Malefyt Ret al. (1991) Interleukin-10 inhibits cytokines synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes . J Exp Med174: 1209-1220 .
12.
Nicholson LB , Kuchroo VK. (1996) Manipulation of the Th1/Th2 balance in autoimmune diseases . Curr Opin Immunol8: 837-842 .
13.
Liblau RS , Singer SM , McDevitt HO. (1995) Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune disease . Immunol Today16: 34-38 .
14.
Rott O , Fleisher B , Cash B. (1994) Interleukin-10 prevents experimental allergic encephalomyelitis in rats . Eur J Immunol24: 1434-1440 .
15.
Khoury SJ , Hancock WW , Weiner HL. (1992) Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with down-regulation of inflammatory cytokines and differential upregulation of transforming growths factor b, interleukin-4 and prostaglandin E expression in the brain . J Exp Med176: 1355-1364 .
16.
Poser CMet al. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols . Ann Neurol13: 227-231 .
17.
Deibler GE , Martenson RE , Kies MW. (1972) Large scale preparation of myelin basic protein from central nervous tissue of several mammalian species . Prep Bioch2: 139-165 .
18.
Santos LMBet al. (1994) Oral Tolerance to myelin basic protein induces regulatory TGFb secreting T cells in Peyer's patches . Cell Immunol157: 439-447 .
19.
Mosmann TR , Sad S. (1996) The expanding universe of T-cell subsets: Th1, Th2 and more . Immunology Today138: 138-146 .
20.
Seder RA , Paul WE. (1994) Acquisition of lymphokine-producing phenotypes by CD4+ T cells . Ann Rev Immunol12: 635-673 .
21.
D'Orazio TJ , Niederkon JY. (1998) A novel role of TGFb and IL 10 in the induction of immune privilege . J Immunol160: 2089-2098 .
22.
Hafler DA , Weiner HL. (1989) Multiple sclerosis a CNS and systemic autoimmune disease . Immunology Today10: 104-107 .
Probert Let al. (1995) Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha . Proc Natl Acad Sci USA92: 11294-11298 .
25.
Brod SAet al. (1995) Decreased CD3 mediated interferon g production in relapsing-remitting multiple sclerosis . Ann Neurol37: 546-549 .
26.
Link Jet al. (1994) Organ-specific autoantigens induce interferon gamma and interleukin 4 mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis . Neurology44: 728-734 .
27.
Willenborg DOet al. (1996) IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced auto-immune encephalomyelitis . J Immunol157: 3223-3227 .
28.
Haremans Het al. (1996) Chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice: enhancement by monoclonal antibodies against interferon-gamma . Eur J Immunol26: 2393-2398 .
29.
Ferber IAet al. (1996) Mice with a disrupted IFNg gene are susceptible to the induction of experimental auto-immune encephalomyelitis (EAE) . J Immunol156: 5-7 .
30.
Kennedy MK , Torrence DS , Pichia KS , Mohler KM. (1992) Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery . J Immunol149: 2496-2505 .
31.
Musette Pet al. (1996) The pattern of reproduction of cytokine mRNA is markedly altered at the onset of Multiple Sclerosis . Res Immunol147: 435-441 .
32.
Rieckmann Pet al. (1994) Cytokine mRNA levels in mononuclear blood cells from patients with active Multiple Sclerosis . Neurology44: 1523-1526 .
33.
Chen Yet al. (1994) Regulatory T cell clones induced by oral tolerance: suppression of experimental autoimmune encephalomyelitis . Science265: 1237-1240 .
34.
Mokhtarian Fet al. (1994) Defective production of anti-inflammatory cytokine TGFb by T cell lines of patients with active multiple sclerosis . J Immunol152: 6003-6011 .
35.
Correale Jet al. (1995) Patterns of cytokine secretion by autoreactive proteolipid protein specific T cell clones during the course of multiple sclerosis . J Immunol154: 2959-2968 .
36.
Miller Aet al. (1993) Epitopes of myelin basic protein that trigger TGF b release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression . J Immunol151: 7307-7315 .
