| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
In experimental transplantation, blockade of CD40-CD40 ligand (CD40L) interactions has proved effective at permitting long-term graft survival and has recently been approved for clinical evaluation. We show that CD4+ T cell-mediated rejection is prevented by anti-CD40L mAb therapy but that CD8+ T cells remain fully functional. Furthermore, blocking CD40L interactions has no effect on CD8+ T cell activation, proliferation, differentiation, homing to the target allograft, or cytokine production. We conclude that CD40L is not an important costimulatory molecule for CD8+ T cell activation and that following transplantation donor APC can activate recipient CD8+ T cells directly without first being primed by CD4+ T cells.
This article has been cited by other articles:
|
|
 |
|
  X. Yuan, M. J. Ansari, F. D'Addio, J. Paez-Cortez, I. Schmitt, M. Donnarumma, O. Boenisch, X. Zhao, J. Popoola, M. R. Clarkson, et al. Targeting Tim-1 to overcome resistance to transplantation tolerance mediated by CD8 T17 cells PNAS, June 30, 2009; 106(26): 10734 - 10739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Gondek, V. DeVries, E. C. Nowak, L.-F. Lu, K. A. Bennett, Z. A. Scott, and R. J. Noelle Transplantation Survival Is Maintained by Granzyme B+ Regulatory Cells and Adaptive Regulatory T Cells J. Immunol., October 1, 2008; 181(7): 4752 - 4760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Haspot, T. Fehr, C. Gibbons, G. Zhao, T. Hogan, T. Honjo, G. J. Freeman, and M. Sykes Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway Blood, September 1, 2008; 112(5): 2149 - 2155. [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]
|
|
|
|
|
|
Y. Zhai, Y. Wang, Z. Wu, and J. W. Kupiec-Weglinski Defective Alloreactive CD8 T Cell Function and Memory Response in Allograft Recipients in the Absence of CD4 Help J. Immunol., October 1, 2007; 179(7): 4529 - 4534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Horne, M. A. Koester, K. Jayashankar, K. E. Lunsford, H. L. Dziema, and G. L. Bumgardner Disparate Primary and Secondary Allospecific CD8+ T Cell Cytolytic Effector Function in the Presence or Absence of Host CD4+ T Cells J. Immunol., July 1, 2007; 179(1): 80 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Ford, B. H. Koehn, M. E. Wagener, W. Jiang, S. Gangappa, T. C. Pearson, and C. P. Larsen Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation J. Exp. Med., February 19, 2007; 204(2): 299 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. D. Jones, M. Carvalho-Gaspar, S. Luo, M. O. Brook, L. Martin, and K. J. Wood Effector and Memory CD8+ T Cells Can Be Generated in Response to Alloantigen Independently of CD4+ T Cell Help J. Immunol., February 15, 2006; 176(4): 2316 - 2323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Nanji, W. W. Hancock, B. Luo, C. D. Schur, R. L. Pawlick, L. F. Zhu, C. C. Anderson, and A.M. J. Shapiro Costimulation Blockade of Both Inducible Costimulator and CD40 Ligand Induces Dominant Tolerance to Islet Allografts and Prevents Spontaneous Autoimmune Diabetes in the NOD Mouse Diabetes, January 1, 2006; 55(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W Chalermskulrat, K P McKinnon, W J Brickey, I P Neuringer, R C Park, D G Sterka, B R Long, P McNeillie, R J Noelle, J P Ting, et al. Combined donor specific transfusion and anti-CD154 therapy achieves airway allograft tolerance Thorax, January 1, 2006; 61(1): 61 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Lunsford, M. A. Koester, A. M. Eiring, P. H. Horne, D. Gao, and G. L. Bumgardner Targeting LFA-1 and CD154 Suppresses the In Vivo Activation and Development of Cytolytic (CD4-Independent) CD8+ T Cells J. Immunol., December 15, 2005; 175(12): 7855 - 7866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Karim, G. Feng, K. J. Wood, and A. R. Bushell CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulation Blood, June 15, 2005; 105(12): 4871 - 4877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yamada, A. D. Salama, M. Sho, N. Najafian, T. Ito, J. P. Forman, R. Kewalramani, S. Sandner, H. Harada, M. R. Clarkson, et al. CD70 Signaling Is Critical for CD28-Independent CD8+ T Cell-Mediated Alloimmune Responses In Vivo J. Immunol., February 1, 2005; 174(3): 1357 - 1364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kreisel, A. M. Krasinskas, A. S. Krupnick, A. E. Gelman, K. R. Balsara, S. H. Popma, M. Riha, A. M. Rosengard, L. A. Turka, and B. R. Rosengard Vascular Endothelium Does Not Activate CD4+ Direct Allorecognition in Graft Rejection J. Immunol., September 1, 2004; 173(5): 3027 - 3034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. van Maurik, B. F. de St. Groth, K. J. Wood, and N. D. Jones Dependency of Direct Pathway CD4+ T Cells on CD40-CD154 Costimulation Is Determined by Nature and Microenvironment of Primary Contact with Alloantigen J. Immunol., February 15, 2004; 172(4): 2163 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Chalermskulrat, I. P. Neuringer, W. J. Brickey, N. J. Felix, S. H. Randell, J. P. Ting, and R. M. Aris Hierarchical Contributions of Allorecognition Pathways in Chronic Lung Rejection Am. J. Respir. Crit. Care Med., April 1, 2003; 167(7): 999 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Blaha, S. Bigenzahn, Z. Koporc, M. Schmid, F. Langer, E. Selzer, H. Bergmeister, F. Wrba, J. Kurtz, C. Kiss, et al. The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade Blood, April 1, 2003; 101(7): 2886 - 2893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Phillips, T. G. Markees, J. P. Mordes, D. L. Greiner, and A. A. Rossini Blockade of CD40-Mediated Signaling Is Sufficient for Inducing Islet But Not Skin Transplantation Tolerance J. Immunol., March 15, 2003; 170(6): 3015 - 3023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhai, L. Meng, R. W. Busuttil, M. H. Sayegh, and J. W. Kupiec-Weglinski Activation of Alloreactive CD8+ T Cells Operates Via CD4-Dependent and CD4-Independent Mechanisms and Is CD154 Blockade Sensitive J. Immunol., March 15, 2003; 170(6): 3024 - 3028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kreisel, A. S. Krupnick, K. R. Balsara, M. Riha, A. E. Gelman, S. H. Popma, W. Y. Szeto, L. A. Turka, and B. R. Rosengard Mouse Vascular Endothelium Activates CD8+ T Lymphocytes in a B7-Dependent Fashion J. Immunol., December 1, 2002; 169(11): 6154 - 6161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. v. Maurik, M. Herber, K. J. Wood, and N. D. Jones Cutting Edge: CD4+CD25+ Alloantigen-Specific Immunoregulatory Cells That Can Prevent CD8+ T Cell-Mediated Graft Rejection: Implications for Anti-CD154 Immunotherapy J. Immunol., November 15, 2002; 169(10): 5401 - 5404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhai, L. Meng, F. Gao, R. W. Busuttil, and J. W. Kupiec-Weglinski Allograft Rejection by Primed/Memory CD8+ T Cells Is CD154 Blockade Resistant: Therapeutic Implications for Sensitized Transplant Recipients J. Immunol., October 15, 2002; 169(8): 4667 - 4673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhai, X.-D. Shen, F. Gao, A. J. Coito, B. A. Wasowska, A. Salama, I. Schmitt, R. W. Busuttil, M. H. Sayegh, and J. W. Kupiec-Weglinski The CD154-CD40 T Cell Costimulation Pathway Is Required for Host Sensitization of CD8+ T Cells by Skin Grafts Via Direct Antigen Presentation J. Immunol., August 1, 2002; 169(3): 1270 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Demirci, W. Gao, X. X. Zheng, T. R. Malek, T. B. Strom, and X. C. Li On CD28/CD40 Ligand Costimulation, Common {gamma}-Chain Signals, and the Alloimmune Response J. Immunol., May 1, 2002; 168(9): 4382 - 4390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Fischbein, J. Yun, H. Laks, Y. Irie, M. C. Fishbein, B. Bonavida, and A. Ardehali Role of CD8+ lymphocytes in chronic rejection of transplanted hearts J. Thorac. Cardiovasc. Surg., April 1, 2002; 123(4): 803 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
T. R. Jones, J. Ha, M. A. Williams, A. B. Adams, M. M. Durham, P. A. Rees, S. R. Cowan, T. C. Pearson, and C. P. Larsen The Role of the IL-2 Pathway in Costimulation Blockade-Resistant Rejection of Allografts J. Immunol., February 1, 2002; 168(3): 1123 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Guo, J. Wang, L. Meng, Q. Wu, O. Kim, J. Hart, G. He, P. Zhou, J. R. Thistlethwaite Jr., M.-L. Alegre, et al. Cutting Edge: Membrane Lymphotoxin Regulates CD8+ T Cell-Mediated Intestinal Allograft Rejection J. Immunol., November 1, 2001; 167(9): 4796 - 4800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ferrari-Lacraz, X. X. Zheng, Y. S. Kim, Y. Li, W. Maslinski, X. C. Li, and T. B. Strom An Antagonist IL-15/Fc Protein Prevents Costimulation Blockade-Resistant Rejection J. Immunol., September 15, 2001; 167(6): 3478 - 3485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Taylor, C. J. Lees, H. Waldmann, R. J. Noelle, and B. R. Blazar Requirements for the promotion of allogeneic engraftment by anti-CD154 (anti-CD40L) monoclonal antibody under nonmyeloablative conditions Blood, July 15, 2001; 98(2): 467 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Ensminger, B. M. Spriewald, H. V. Sorensen, O. Witzke, E. G. Flashman, A. Bushell, P. J. Morris, M. L. Rose, A. Rahemtulla, and K. J. Wood Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation J. Immunol., July 1, 2001; 167(1): 532 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Qian, F. Boisgerault, G. Benichou, and M. R. Dana Blockade of CD40-CD154 Costimulatory Pathway Promotes Survival of Allogeneic Corneal Transplants Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 987 - 994. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ito, J. Kurtz, J. Shaffer, and M. Sykes CD4 T Cell-Mediated Alloresistance to Fully MHC-Mismatched Allogeneic Bone Marrow Engraftment Is Dependent on CD40-CD40 Ligand Interactions, and Lasting T Cell Tolerance Is Induced by Bone Marrow Transplantation with Initial Blockade of this Pathway J. Immunol., March 1, 2001; 166(5): 2970 - 2981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Gorbachev, P. S. Heeger, and R. L. Fairchild CD4+ and CD8+ T Cell Priming for Contact Hypersensitivity Occurs Independently of CD40-CD154 Interactions J. Immunol., February 15, 2001; 166(4): 2323 - 2332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Fischbein, A. Ardehali, J. Yun, S. Schoenberger, H. Laks, Y. Irie, P. Dempsey, G. Cheng, M. C. Fishbein, and B. Bonavida CD40 Signaling Replaces CD4+ Lymphocytes and Its Blocking Prevents Chronic Rejection of Heart Transplants J. Immunol., December 15, 2000; 165(12): 7316 - 7322. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
