T-cell-directed therapies in inflammatory bowel diseases

被引:41
作者
Monteleone, Giovanni [1 ]
Caprioli, Flavio [2 ]
机构
[1] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy
[2] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Unit Gastroenterol 2, Milan, Italy
关键词
Crohn's disease; cytokine; inflammatory bowel disease (IBD); interleukin; T-cell; ulcerative colitis; tumour necrosis factor (TNF); ACTIVE CROHNS-DISEASE; MONOCLONAL-ANTIBODY CA2; NECROSIS-FACTOR-ALPHA; ULCERATIVE-COLITIS; MAINTENANCE THERAPY; RANDOMIZED-TRIAL; INFLIXIMAB; APOPTOSIS; LYMPHOCYTES; CYCLOSPORINE;
D O I
10.1042/CS20100027
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Gut inflammation occurring in patients with IBDs (inflammatory bowel diseases) is associated with exaggerated and poorly controlled T-cell-mediated immune responses, which are directed against normal components of the gut flora. T-cells accumulate in the inflamed gut of IBD patients as a result of multiple mechanisms, including enhanced recruitment of cells from the bloodstream, sustained cell cycling and diminished susceptibility of cells to undergo apoptosis. Activated T-cells produce huge amounts of cytokines, which contribute to amplify and sustain the ongoing mucosal inflammation. Strategies aimed at interfering with T-cell accumulation and/or function in the gut have been employed with clinical success in patients with IBDs. In the present article, we review the available results showing that T-cell-directed therapies are useful to dampen the tissue-damaging immune response in IBDs.
引用
收藏
页码:707 / 715
页数:9
相关论文
共 76 条
[1]   Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation:: Evidence in Crohn disease and experimental colitis in vivo [J].
Atreya, R ;
Mudter, J ;
Finotto, S ;
Müllberg, J ;
Jostock, T ;
Wirtz, S ;
Schütz, M ;
Bartsch, B ;
Holtmann, M ;
Becker, C ;
Strand, D ;
Czaja, J ;
Schlaak, JF ;
Lehr, HA ;
Autschbach, F ;
Schürmann, G ;
Nishimoto, N ;
Yoshizaki, K ;
Ito, H ;
Kishimoto, T ;
Galle, PR ;
Rose-John, S ;
Neurath, MF .
NATURE MEDICINE, 2000, 6 (05) :583-588
[2]   Regulatory T Cells Reinforce Intestinal Homeostasis [J].
Barnes, Michael J. ;
Powrie, Fiona .
IMMUNITY, 2009, 31 (03) :401-411
[3]   Prospective Randomized Open-label Multicenter Phase I/II Dose Escalation Trial of Visilizumab (HuM291) in Severe Steroid-refractory Ulcerative Colitis [J].
Baumgart, Daniel C. ;
Targan, Stephan R. ;
Dignass, Axel U. ;
Mayer, Lloyd ;
van Assche, Gert ;
Hommes, Daan W. ;
Hanauer, Stephen B. ;
Mahadevan, Uma ;
Reinisch, Walter ;
Plevy, Scott E. ;
Salzberg, Bruce A. ;
Buchman, Alan L. ;
Mechkov, Grigor M. ;
Krastev, Zahariy A. ;
Lowder, James N. ;
Frankel, Matthew B. ;
Sandborn, William J. .
INFLAMMATORY BOWEL DISEASES, 2010, 16 (04) :620-629
[4]   Early preservation of effector functions followed by eventual T cell memory depletion: a model for the delayed onset of the effect of thiopurines [J].
Ben-Horin, S. ;
Goldstein, I. ;
Fudim, E. ;
Picard, O. ;
Yerushalmi, Z. ;
Barshack, I. ;
Bank, I. ;
Goldschmid, Y. ;
Bar Meir, S. ;
Mayer, L. ;
Chowers, Y. .
GUT, 2009, 58 (03) :396-403
[5]   Lamina propria T cells in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis [J].
Boirivant, M ;
Marini, M ;
Di Felice, G ;
Pronio, AM ;
Montesani, C ;
Tersigni, R ;
Strober, W .
GASTROENTEROLOGY, 1999, 116 (03) :557-565
[6]   Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease [J].
Brand, S. .
GUT, 2009, 58 (08) :1152-1167
[7]   Ciclosporin use in acute ulcerative colitis: a long-term experience [J].
Campbell, S ;
Travis, S ;
Jewell, D .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2005, 17 (01) :79-84
[8]   Transcriptional and post-translational regulation of Flip, an inhibitor of Fas-mediated apoptosis, in human gut inflammation [J].
Caprioli, F. ;
Stolfi, C. ;
Caruso, R. ;
Fina, D. ;
Sica, G. ;
Biancone, L. ;
Pallone, F. ;
Monteleone, G. .
GUT, 2008, 57 (12) :1674-1680
[9]   A humanized non-FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease [J].
Carpenter, PA ;
Appelbaum, FR ;
Corey, L ;
Deeg, HJ ;
Doney, K ;
Gooley, T ;
Krueger, J ;
Martin, P ;
Pavlovic, S ;
Sanders, J ;
Slattery, J ;
Levitt, D ;
Storb, R ;
Woolfrey, A ;
Anasetti, C .
BLOOD, 2002, 99 (08) :2712-2719
[10]   Adalimumab for the treatment of fistulas in patients with Crohn's disease [J].
Colombel, J-F ;
Schwartz, D. A. ;
Sandborn, W. J. ;
Kamm, M. A. ;
D'Haens, G. ;
Rutgeerts, P. ;
Enns, R. ;
Panaccione, R. ;
Schreiber, S. ;
Li, J. ;
Kent, J. D. ;
Lomax, K. G. ;
Pollack, P. F. .
GUT, 2009, 58 (07) :940-948