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Cutting Edge |
Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611
Autoreactive CD4+ T cells exist in normal individuals and retain the capacity to initiate autoimmune disease. The current study investigates the role of CD4+CD25+ T-regulatory (TR) cells during autoimmune disease using the CD4+ T cell-dependent myelin oligodendrocyte glycoprotein (MOG)-specific experimental autoimmune encephalomyelitis model of multiple sclerosis. In vitro, TR cells effectively inhibited both the proliferation of and cytokine production by MOG35–55-specific Th1 cells. In vivo, adoptive transfer of TR cells conferred significant protection from clinical experimental autoimmune encephalomyelitis which was associated with normal activation of autoreactive Th1 cells, but an increased frequency of MOG35–55-specific Th2 cells and decreased CNS infiltration. Lastly, transferred TR cells displayed an enhanced ability to traffic to the peripheral lymph nodes and expressed increased levels of the adhesion molecules ICAM-1 and P-selectin that may promote functional interactions with target T cells. Collectively, these findings suggest that TR cells contribute notably to the endogenous mechanisms that regulate actively induced autoimmune disease.
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N. Beyersdorf, S. Gaupp, K. Balbach, J. Schmidt, K. V. Toyka, C.-H. Lin, T. Hanke, T. Hunig, T. Kerkau, and R. Gold Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis J. Exp. Med., August 1, 2005; 202(3): 445 - 455. [Abstract] [Full Text] [PDF]
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G. Matarese, P. B. Carrieri, A. La Cava, F. Perna, V. Sanna, V. De Rosa, D. Aufiero, S. Fontana, and S. Zappacosta Leptin increase in multiple sclerosis associates with reduced number of CD4+CD25+ regulatory T cells PNAS, April 5, 2005; 102(14): 5150 - 5155. [Abstract] [Full Text] [PDF]
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 D. Lundsgaard, T. L. Holm, L. Hornum, and H. Markholst In Vivo Control of Diabetogenic T-Cells by Regulatory CD4+CD25+ T-Cells Expressing Foxp3 Diabetes, April 1, 2005; 54(4): 1040 - 1047. [Abstract] [Full Text] [PDF]
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S. Schif-Zuck, J. Westermann, N. Netzer, Y. Zohar, M. Meiron, G. Wildbaum, and N. Karin Targeted Overexpression of IL-18 Binding Protein at the Central Nervous System Overrides Flexibility in Functional Polarization of Antigen-Specific Th2 Cells J. Immunol., April 1, 2005; 174(7): 4307 - 4315. [Abstract] [Full Text] [PDF]
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M. R. Walker, B. D. Carson, G. T. Nepom, S. F. Ziegler, and J. H. Buckner De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells PNAS, March 15, 2005; 102(11): 4103 - 4108. [Abstract] [Full Text] [PDF]
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A. Loughry, S. Fairchild, N. Athanasou, J. Edwards, and F. C. Hall Inflammatory arthritis and dermatitis in thymectomized, CD25+ cell-depleted adult mice Rheumatology, March 1, 2005; 44(3): 299 - 308. [Abstract] [Full Text] [PDF]
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D. J. Mekala and T. L. Geiger Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes Blood, March 1, 2005; 105(5): 2090 - 2092. [Abstract] [Full Text] [PDF]
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A. Matejuk, C. Hopke, A. A. Vandenbark, P. D. Hurn, and H. Offner Middle-Age Male Mice Have Increased Severity of Experimental Autoimmune Encephalomyelitis and Are Unresponsive to Testosterone Therapy J. Immunol., February 15, 2005; 174(4): 2387 - 2395. [Abstract] [Full Text] [PDF]
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P. E. Rao, A. L. Petrone, and P. D. Ponath Differentiation and Expansion of T Cells with Regulatory Function from Human Peripheral Lymphocytes by Stimulation in the Presence of TGF-{beta} J. Immunol., February 1, 2005; 174(3): 1446 - 1455. [Abstract] [Full Text] [PDF]
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N. Taylor, K. McConnachie, C. Calder, R. Dawson, A. Dick, J. D. Sedgwick, and J. Liversidge Enhanced Tolerance to Autoimmune Uveitis in CD200-Deficient Mice Correlates with a Pronounced Th2 Switch in Response to Antigen Challenge J. Immunol., January 1, 2005; 174(1): 143 - 154. [Abstract] [Full Text] [PDF]
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T. Kubo, R. D. Hatton, J. Oliver, X. Liu, C. O. Elson, and C. T. Weaver Regulatory T Cell Suppression and Anergy Are Differentially Regulated by Proinflammatory Cytokines Produced by TLR-Activated Dendritic Cells J. Immunol., December 15, 2004; 173(12): 7249 - 7258. [Abstract] [Full Text] [PDF]
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J. Kipnis, H. Avidan, R. R. Caspi, and M. Schwartz Dual effect of CD4+CD25+ regulatory T cells in neurodegeneration: A dialogue with microglia PNAS, October 5, 2004; 101(suppl_2): 14663 - 14669. [Abstract] [Full Text] [PDF]
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N. Sarween, A. Chodos, C. Raykundalia, M. Khan, A. K. Abbas, and L. S. K. Walker CD4+CD25+ Cells Controlling a Pathogenic CD4 Response Inhibit Cytokine Differentiation, CXCR-3 Expression, and Tissue Invasion J. Immunol., September 1, 2004; 173(5): 2942 - 2951. [Abstract] [Full Text] [PDF]
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M. J. Polanczyk, B. D. Carson, S. Subramanian, M. Afentoulis, A. A. Vandenbark, S. F. Ziegler, and H. Offner Cutting Edge: Estrogen Drives Expansion of the CD4+CD25+ Regulatory T Cell Compartment J. Immunol., August 15, 2004; 173(4): 2227 - 2230. [Abstract] [Full Text] [PDF]
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M. R. Ehrenstein, J. G. Evans, A. Singh, S. Moore, G. Warnes, D. A. Isenberg, and C. Mauri Compromised Function of Regulatory T Cells in Rheumatoid Arthritis and Reversal by Anti-TNF{alpha} Therapy J. Exp. Med., August 2, 2004; 200(3): 277 - 285. [Abstract] [Full Text] [PDF]
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Y. E. Latchman, S. C. Liang, Y. Wu, T. Chernova, R. A. Sobel, M. Klemm, V. K. Kuchroo, G. J. Freeman, and A. H. Sharpe PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells PNAS, July 20, 2004; 101(29): 10691 - 10696. [Abstract] [Full Text] [PDF]
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A. C. Anderson, J. Reddy, R. Nazareno, R. A. Sobel, L. B. Nicholson, and V. K. Kuchroo IL-10 Plays an Important Role in the Homeostatic Regulation of the Autoreactive Repertoire in Naive Mice J. Immunol., July 15, 2004; 173(2): 828 - 834. [Abstract] [Full Text] [PDF]
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 J. Kipnis, M. Cardon, H. Avidan, G. M. Lewitus, S. Mordechay, A. Rolls, Y. Shani, and M. Schwartz Dopamine, through the Extracellular Signal-Regulated Kinase Pathway, Downregulates CD4+CD25+ Regulatory T-Cell Activity: Implications for Neurodegeneration J. Neurosci., July 7, 2004; 24(27): 6133 - 6143. [Abstract] [Full Text] [PDF]
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S. Vigouroux, E. Yvon, E. Biagi, and M. K. Brenner Antigen-induced regulatory T cells Blood, July 1, 2004; 104(1): 26 - 33. [Abstract] [Full Text] [PDF]
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B. K. Choi, J. S. Bae, E. M. Choi, W. J. Kang, S. Sakaguchi, D. S. Vinay, and B. S. Kwon 4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells J. Leukoc. Biol., May 1, 2004; 75(5): 785 - 791. [Abstract] [Full Text] [PDF]
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A. P. Kohm, J. S. Williams, and S. D. Miller Cutting Edge: Ligation of the Glucocorticoid-Induced TNF Receptor Enhances Autoreactive CD4+ T Cell Activation and Experimental Autoimmune Encephalomyelitis J. Immunol., April 15, 2004; 172(8): 4686 - 4690. [Abstract] [Full Text] [PDF]
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V. Viglietta, C. Baecher-Allan, H. L. Weiner, and D. A. Hafler Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis J. Exp. Med., April 5, 2004; 199(7): 971 - 979. [Abstract] [Full Text] [PDF]
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S. Suvas, A. K. Azkur, B. S. Kim, U. Kumaraguru, and B. T. Rouse CD4+CD25+ Regulatory T Cells Control the Severity of Viral Immunoinflammatory Lesions J. Immunol., April 1, 2004; 172(7): 4123 - 4132. [Abstract] [Full Text] [PDF]
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X. Zhang, D. N. Koldzic, L. Izikson, J. Reddy, R. F. Nazareno, S. Sakaguchi, V. K. Kuchroo, and H. L. Weiner IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells Int. Immunol., February 1, 2004; 16(2): 249 - 256. [Abstract] [Full Text] [PDF]
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 Y. Wang, M. Lobigs, E. Lee, and A. Mullbacher CD8+ T Cells Mediate Recovery and Immunopathology in West Nile Virus Encephalitis J. Virol., December 15, 2003; 77(24): 13323 - 13334. [Abstract] [Full Text] [PDF]
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B. E. Theien, C. L. Vanderlugt, C. Nickerson-Nutter, M. Cornebise, D. M. Scott, S. J. Perper, E. T. Whalley, and S. D. Miller Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE Blood, December 15, 2003; 102(13): 4464 - 4471. [Abstract] [Full Text] [PDF]
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D. Avichezer, R. S. Grajewski, C.-C. Chan, M. J. Mattapallil, P. B. Silver, J. A. Raber, G. I. Liou, B. Wiggert, G. M. Lewis, L. A. Donoso, et al. An Immunologically Privileged Retinal Antigen Elicits Tolerance: Major Role for Central Selection Mechanisms J. Exp. Med., December 1, 2003; 198(11): 1665 - 1676. [Abstract] [Full Text] [PDF]
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S. Vigouroux, E. Yvon, H.-J. Wagner, E. Biagi, G. Dotti, U. Sili, C. Lira, C. M. Rooney, and M. K. Brenner Induction of Antigen-Specific Regulatory T Cells following Overexpression of a Notch Ligand by Human B Lymphocytes J. Virol., October 15, 2003; 77(20): 10872 - 10880. [Abstract] [Full Text] [PDF]
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S. Gregori, N. Giarratana, S. Smiroldo, and L. Adorini Dynamics of Pathogenic and Suppressor T Cells in Autoimmune Diabetes Development J. Immunol., October 15, 2003; 171(8): 4040 - 4047. [Abstract] [Full Text] [PDF]
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 D. L. Sewell, E. K. Reinke, D. O. Co, L. H. Hogan, R. B. Fritz, M. Sandor, and Z. Fabry Infection with Mycobacterium bovis BCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis Clin. Vaccine Immunol., July 1, 2003; 10(4): 564 - 572. [Abstract] [Full Text] [PDF]
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K. C. Dowdell, D. J. Cua, E. Kirkman, and S. A. Stohlman NK Cells Regulate CD4 Responses Prior to Antigen Encounter J. Immunol., July 1, 2003; 171(1): 234 - 239. [Abstract] [Full Text] [PDF]
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