| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Interaction in Acute Allograft Rejection and CD40L-Independent Chronic Allograft Rejection1
* Institut National de la Santé et de la Recherche Médicale Unit 437, and Institut de Transplantation et de Recherche en Transplantation, Nantes, France;
Service d’Anatomie Pathologique du Centre Hospitalier Régional Universitaire de Nantes, Nantes, France;
Plateforme de Microscopie Confocale et Imagerie de l’IFR26, Faculté de Médecine, Nantes, France; and Departments of
Pathology and Laboratory Medicine and
¶ Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
We analyzed the role of TNF-related activation-induced cytokine (TRANCE), a member of the TNF family expressed on activated T cells that shares functional properties with CD40L, and its receptor-activating NF-
B (RANK) which is mostly expressed on mature dendritic cells, during allogenic responses in vivo using a rodent heart allograft model. TRANCE mRNA was strongly up-regulated in acutely rejected allografts on days 4 and 5 posttransplantation whereas RANK was detected as early as day 1 but did not show further up-regulation during the first week. Immunofluoresence analyses of heart allografts showed that 80 and 100% of TRANCE and RANK-expressing cells were T cells and APCs, respectively. We show for the first time that short-term TRANCE blockade using a mouse RANKIg fusion molecule can significantly prolong heart allograft survival in both rat and mouse models. Similarly, rat heart allografts transduced with a RANKIg encoding recombinant adenovirus exhibited a significant prolongation of survival (14.3 vs 7.6 days, p < 0.0001). However, TRANCE blockade using RANKIg did not appear to inhibit allogeneic T and B cell priming humoral responses against RANKIg. Interestingly, TRANCE blockade induced strong up-regulation of CD40 ligand (CD40L) mRNA in allografts. Combined CD40L and TRANCE blockade resulted in significantly decreased chronic allograft rejection lesions as well as allogeneic humoral responses compared with CD40L blockade alone. We conclude that TRANCE-RANK interactions play an important role during acute allograft rejection and that CD40L-independent allogeneic immune responses can be, at least in part, dependent on the TRANCE pathway of costimulation.
This article has been cited by other articles:
|
|
 |
|
  F. Lamoureux, G. Picarda, J. Rousseau, C. Gourden, S. Battaglia, C. Charrier, B. Pitard, D. Heymann, and F. Redini Therapeutic efficacy of soluble receptor activator of nuclear factor-{kappa}B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma Mol. Cancer Ther., October 1, 2008; 7(10): 3389 - 3398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Ford, M. E. Wagener, S. S. Hanna, T. C. Pearson, A. D. Kirk, and C. P. Larsen A Critical Precursor Frequency of Donor-Reactive CD4+ T Cell Help Is Required for CD8+ T Cell-Mediated CD28/CD154-Independent Rejection J. Immunol., June 1, 2008; 180(11): 7203 - 7211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guillonneau, C. Seveno, A.-S. Dugast, X.-L. Li, K. Renaudin, F. Haspot, C. Usal, J. Veziers, I. Anegon, and B. Vanhove Anti-CD28 Antibodies Modify Regulatory Mechanisms and Reinforce Tolerance in CD40Ig-Treated Heart Allograft Recipients J. Immunol., December 15, 2007; 179(12): 8164 - 8171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-X. Hubert, C. Voisine, C. Louvet, J.-M. Heslan, A. Ouabed, M. Heslan, and R. Josien Differential Pattern Recognition Receptor Expression but Stereotyped Responsiveness in Rat Spleen Dendritic Cell Subsets J. Immunol., July 15, 2006; 177(2): 1007 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Duplan, G. Beriou, J.-M. Heslan, C. Bruand, P. Dutartre, L. T. Mars, R. S. Liblau, M.-C. Cuturi, and A. Saoudi LF 15-0195 Treatment Protects against Central Nervous System Autoimmunity by Favoring the Development of Foxp3-Expressing Regulatory CD4 T Cells J. Immunol., January 15, 2006; 176(2): 839 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-X. Hubert, C. Voisine, C. Louvet, M. Heslan, and R. Josien Rat Plasmacytoid Dendritic Cells Are an Abundant Subset of MHC Class II+ CD4+CD11b-OX62- and Type I IFN-Producing Cells That Exhibit Selective Expression of Toll-Like Receptors 7 and 9 and Strong Responsiveness to CpG J. Immunol., June 15, 2004; 172(12): 7485 - 7494. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
