The JI Acurri Cytometers
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guillot, C.
Right arrow Articles by Anegon, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guillot, C.
Right arrow Articles by Anegon, I.
The Journal of Immunology, 2000, 164: 5258-5268.
Copyright © 2000 by The American Association of Immunologists

Tolerance to Cardiac Allografts Via Local and Systemic Mechanisms After Adenovirus-Mediated CTLA4Ig Expression1

Cécile Guillot*, Patrick Mathieu*, Hélène Coathalem*, Brigitte Le Mauff*, Maria G. Castro{dagger}, Laurent Tesson*, Claire Usal*, Thomas Laumonier*, Sophie Brouard*, Jean-Paul Soulillou*, Pedro R. Lowenstein{dagger}, Maria Cristina Cuturi* and Ignacio Anegon2,*

* Institut National de la Santé et de la Recherche Médicale U437, Institut de Transplantation et Recherche en Transplantation, Nantes, France; and {dagger} Molecular Medicine and Gene Therapy Unit, Manchester University, Manchester, United Kingdom

Blockade of the CD28/B7 T cell costimulatory pathway prolongs allograft survival and induces tolerance in some animal models. We analyzed the efficacy of a CTLA4Ig-expressing adenovirus in preventing cardiac allorejection in rats, the mechanisms underlying heart transplant acceptance, and whether the effects of CTLA4Ig were restricted to the graft microenvironment or were systemic. CTLA4Ig gene transfer into the myocardium allowed indefinite graft survival (>100 days vs 9 ± 1 days for controls) in 90% of cases, whereas CTLA4Ig protein injected systemically only prolonged cardiac allograft survival (by up to 22 days). CTLA4Ig could be detected in the graft and in the serum for at least 1 year after gene transfer. CTLA4Ig gene transfer induced local intragraft immunomodulation at day 5 after transplantation, as shown by decreased expression of the IL-2R and MHC II Ags; decreased levels of mRNA encoding for IFN-{gamma}, inducible NO synthase, and TGF-ß; and inhibited proliferative responses of graft-infiltrating cells. Systemic immune responses were also down-modulated, as shown by the suppression of Ab production against donor alloantigens and cognate Ags, up to at least 120 days after gene transfer. Alloantigenic and mitogenic proliferative responses of graft-infiltrating cells and total splenocytes were inhibited and were not reversed by IL-2. In contrast, lymph node cells and T cells purified from splenocytes showed normal proliferation. Recipients of long-term grafts treated with adenovirus coding for CTLA4Ig showed organ and donor-specific tolerance. These data show that expression of CTLA4Ig was high and long lasting after adenovirus-mediated gene transfer. This expression resulted in down-modulation of responses against cognate Ags, efficient suppression of local and systemic allograft immune responses, and ultimate induction of donor-specific tolerance.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
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]

Home page
 IOVSHome page
N. Gong, U. Pleyer, K. Vogt, I. Anegon, A. Flugel, H.-D. Volk, and T. Ritter
Local Overexpression of Nerve Growth Factor in Rat Corneal Transplants Improves Allograft Survival
Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1043 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Benigni, S. Tomasoni, L. A. Turka, L. Longaretti, L. Zentilin, M. Mister, A. Pezzotta, N. Azzollini, M. Noris, S. Conti, et al.
Adeno-Associated Virus-Mediated CTLA4Ig Gene Transfer Protects MHC-Mismatched Renal Allografts from Chronic Rejection
J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1665 - 1672.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
J. Li, E. Simeoni, S. Fleury, J. Dudler, E. Fiorini, L. Kappenberger, L. K. von Segesser, and G. Vassalli
Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model.
Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 779 - 783.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Izawa, K. Sano, M. Takehara, M. Inobe, J.-i. Suzuki, H. Imamura, M. Takahashi, U. Ikeda, M. Isobe, and T. Uede
Cre/loxP-mediated CTLA4IgG gene transfer induces clinically relevant immunosuppression via on-off gene recombination in vivo
Cardiovasc Res, January 1, 2006; 69(1): 289 - 297.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
G. Boulday, J. Ashton-Chess, P. Bernard, G. Karam, H. Vie, A. Moreau, D. Minault, K. Lorre, J.-P. Soulillou, and G. Blancho
Association of rapamycin and co-stimulation blockade using anti-B7 antibodies in renal allotransplantation in baboons
Nephrol. Dial. Transplant., July 1, 2004; 19(7): 1752 - 1760.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Guillonneau, C. Louvet, K. Renaudin, J.-M. Heslan, M. Heslan, L. Tesson, C. Vignes, C. Guillot, Y. Choi, L. A. Turka, et al.
The Role of TNF-Related Activation-Induced Cytokine-Receptor Activating NF-{kappa}B Interaction in Acute Allograft Rejection and CD40L-Independent Chronic Allograft Rejection
J. Immunol., February 1, 2004; 172(3): 1619 - 1629.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
T. Hattori, H. Shimokawa, M. Higashi, J. Hiroki, Y. Mukai, K. Kaibuchi, and A. Takeshita
Long-Term Treatment With a Specific Rho-Kinase Inhibitor Suppresses Cardiac Allograft Vasculopathy in Mice
Circ. Res., January 9, 2004; 94(1): 46 - 52.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
G. Vassalli, S. Fleury, J. Li, J.-J. Goy, L. Kappenberger, and L. K. von Segesser
Gene transfer of cytoprotective and immunomodulatory molecules for prevention of cardiac allograft rejection
Eur. J. Cardiothorac. Surg., November 1, 2003; 24(5): 794 - 806.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
P. Mathieu, J. C. Roussel, F. Dagenais, and I. Anegon
Cartilaginous metaplasia and calcification in aortic allograft is associated with transforming growth factor {beta}1 expression
J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1449 - 1454.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
T.-S. Li, H. Ito, K. Kajiwara, and K. Hamano
Long-Term Survival of Xenografted Neonatal Cardiomyocytes by Adenovirus-Mediated CTLA4-Ig Expression and CD40 Blockade
Circulation, October 7, 2003; 108(14): 1760 - 1765.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
C. Braudeau, D. Bouchet, C. Toquet, L. Tesson, S. Menoret, S. Iyer, C. Laboisse, D. Willis, A. Jarry, R. Buelow, et al.
Generation of Heme Oxygenase-1-Transgenic Rats
Experimental Biology and Medicine, May 1, 2003; 228(5): 466 - 471.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Guillot, S. Menoret, C. Guillonneau, C. Braudeau, M. G. Castro, P. Lowenstein, and I. Anegon
Active suppression of allogeneic proliferative responses by dendritic cells after induction of long-term allograft survival by CTLA4Ig
Blood, April 15, 2003; 101(8): 3325 - 3333.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W. Chen, M. S. Ford, K. J. Young, M. I. Cybulsky, and L. Zhang
Role of Double-Negative Regulatory T Cells in Long-Term Cardiac Xenograft Survival
J. Immunol., February 15, 2003; 170(4): 1846 - 1853.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
R. M. Comer, W. J. King, N. Ardjomand, S. Theoharis, A. J. T. George, and D. F. P. Larkin
Effect of Administration of CTLA4-Ig as Protein or cDNA on Corneal Allograft Survival
Invest. Ophthalmol. Vis. Sci., April 1, 2002; 43(4): 1095 - 1103.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Guillot, C. Guillonneau, P. Mathieu, C. A. Gerdes, S. Menoret, C. Braudeau, L. Tesson, K. Renaudin, M. G. Castro, P. R. Lowenstein, et al.
Prolonged Blockade of CD40-CD40 Ligand Interactions by Gene Transfer of CD40Ig Results in Long-Term Heart Allograft Survival and Donor-Specific Hyporesponsiveness, But Does Not Prevent Chronic Rejection
J. Immunol., February 15, 2002; 168(4): 1600 - 1609.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. H. Hammer, G. Schroder, K. Risch, A. Flugel, H.-D. Volk, M. Lehmann, and T. Ritter
Antigen-Dependent Transgene Expression in Kidney Transplantation: A Novel Approach Using Gene-Engineered T Lymphocytes
J. Am. Soc. Nephrol., February 1, 2002; 13(2): 511 - 518.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.