| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,§
*
Laboratory of Experimental Immunology,
Department of Gastroenterology, and
Department of Pathology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium; and
§
Tanox Pharma, Amsterdam, the Netherlands
CD40 ligand (CD40L or CD154), a type II membrane protein with
homology to TNF, is transiently expressed on activated T cells and
known to be important for B cell Ig production and for activation and
differentiation of monocytes and dendritic cells. Both Crohn’s disease
and ulcerative colitis are characterized by local production of
cytokines such as TNF and by an influx of activated lymphocytes into
inflamed mucosa. Herein, we investigated whether CD40L signaling
participates in immune responses in these diseases. Our results
demonstrated that CD40L was expressed on freshly isolated lamina
propria T cells from these patients and was functional to induce IL-12
and TNF production by normal monocytes, especially after IFN-
priming. The inclusion of a blocking mAb to CD40L or CD40 in such
cocultures significantly decreased monocyte IL-12 and TNF production.
Moreover, lamina propria and peripheral blood T cells from these
patients, after in vitro activation with anti-CD3, showed increased
and prolonged expression of CD40L as compared with controls.
Immunohistochemical analyses indicated that the number of
CD40+ and CD40L+ cells was significantly
increased in inflamed mucosa, being B cells/macrophages and
CD4+ T cells, respectively. These findings suggest that
CD40L up-regulation is involved in pathogenic cytokine production in
inflammatory bowel disease and that blockade of CD40-CD40L interactions
may have therapeutic effects for these patients.
This article has been cited by other articles:
|
|
 |
|
  S Brand 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 Gut, August 1, 2009; 58(8): 1152 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Danese, M. Sans, F. Scaldaferri, A. Sgambato, S. Rutella, A. Cittadini, J. M. Pique, J. Panes, J. A. Katz, A. Gasbarrini, et al. TNF-{alpha} Blockade Down-Regulates the CD40/CD40L Pathway in the Mucosal Microcirculation: A Novel Anti-Inflammatory Mechanism of Infliximab in Crohn's Disease J. Immunol., February 15, 2006; 176(4): 2617 - 2624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Sato, T Nakai, N Tamura, S Okamoto, K Matsuoka, A Sakuraba, T Fukushima, T Uede, and T Hibi Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response Gut, September 1, 2005; 54(9): 1254 - 1262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, R. A. Anders, Y. Wang, J. R. Turner, C. Abraham, K. Pfeffer, and Y.-X. Fu The Critical Role of LIGHT in Promoting Intestinal Inflammation and Crohn's Disease J. Immunol., June 15, 2005; 174(12): 8173 - 8182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A L Hart, K Lammers, P Brigidi, B Vitali, F Rizzello, P Gionchetti, M Campieri, M A Kamm, S C Knight, and A J Stagg Modulation of human dendritic cell phenotype and function by probiotic bacteria Gut, November 1, 2004; 53(11): 1602 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Luft, E. Maraskovsky, M. Schnurr, K. Knebel, M. Kirsch, M. Gorner, R. Skoda, A. D. Ho, P. Nawroth, and A. Bierhaus Tuning the volume of the immune response: strength and persistence of stimulation determine migration and cytokine secretion of dendritic cells Blood, August 15, 2004; 104(4): 1066 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Danese, M Sans, and C Fiocchi The CD40/CD40L costimulatory pathway in inflammatory bowel disease Gut, July 1, 2004; 53(7): 1035 - 1043. [Full Text] [PDF]
|
|
|
|
|
|
T. Kawamura, T. Kanai, T. Dohi, K. Uraushihara, T. Totsuka, R. Iiyama, C. Taneda, M. Yamazaki, T. Nakamura, T. Higuchi, et al. Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation J. Immunol., May 15, 2004; 172(10): 6388 - 6397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Danese, J A Katz, S Saibeni, A Papa, A Gasbarrini, M Vecchi, and C Fiocchi Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients Gut, October 1, 2003; 52(10): 1435 - 1441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C M Gelbmann, S N Leeb, D Vogl, M Maendel, H Herfarth, J Scholmerich, W Falk, and G Rogler Inducible CD40 expression mediates NF{kappa}B activation and cytokine secretion in human colonic fibroblasts Gut, October 1, 2003; 52(10): 1448 - 1456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A J Stagg, A L Hart, S C Knight, and M A Kamm The dendritic cell: its role in intestinal inflammation and relationship with gut bacteria Gut, October 1, 2003; 52(10): 1522 - 1529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Marhaba, M. Bourouba, and M. Zoller CD44v7 interferes with activation-induced cell death by up-regulation of anti-apoptotic gene expression J. Leukoc. Biol., July 1, 2003; 74(1): 135 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Chase, M. Bond, M. F. Crook, and A. C. Newby Role of Nuclear Factor-{kappa}B Activation in Metalloproteinase-1, -3, and -9 Secretion by Human Macrophages In Vitro and Rabbit Foam Cells Produced In Vivo Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 765 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nakase, K. Okazaki, Y. Tabata, M. Ozeki, N. Watanabe, M. Ohana, S. Uose, K. Uchida, T. Nishi, M. Mastuura, et al. New Cytokine Delivery System Using Gelatin Microspheres Containing Interleukin-10 for Experimental Inflammatory Bowel Disease J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 59 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Boon, H. P. M. Brok, J. Bauer, A. Ortiz-Buijsse, M. M. Schellekens, S. Ramdien-Murli, E. Blezer, M. van Meurs, J. Ceuppens, M. de Boer, et al. Prevention of Experimental Autoimmune Encephalomyelitis in the Common Marmoset (Callithrix jacchus) Using a Chimeric Antagonist Monoclonal Antibody Against Human CD40 Is Associated with Altered B Cell Responses J. Immunol., September 1, 2001; 167(5): 2942 - 2949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lettesjo, G. P. Burd, and R. A. Mageed CD4+ T Lymphocytes with Constitutive CD40 Ligand in Preautoimmune (NZB NZW)F1 Lupus-Prone Mice: Phenotype and Possible Role in Autoreactivity J. Immunol., October 1, 2000; 165(7): 4095 - 4104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Liu, K. Geboes, S. Colpaert, L. Overbergh, C. Mathieu, H. Heremans, M. de Boer, L. Boon, G. D'Haens, P. Rutgeerts, et al. Prevention of Experimental Colitis in SCID Mice Reconstituted with CD45RBhigh CD4+ T Cells by Blocking the CD40-CD154 Interactions J. Immunol., June 1, 2000; 164(11): 6005 - 6014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Liu, K. Geboes, S. Colpaert, G. R. D'Haens, P. Rutgeerts, and J. L. Ceuppens IL-15 Is Highly Expressed in Inflammatory Bowel Disease and Regulates Local T Cell-Dependent Cytokine Production J. Immunol., April 1, 2000; 164(7): 3608 - 3615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Moodycliffe, V. Shreedhar, S. E. Ullrich, J. Walterscheid, C. Bucana, M. L. Kripke, and L. Flores-Romo CD40-CD40 Ligand Interactions In Vivo Regulate Migration of Antigen-bearing Dendritic Cells from the Skin to Draining Lymph Nodes J. Exp. Med., June 6, 1999; 191(11): 2011 - 2020. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
