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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.
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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]
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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]
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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]
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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]
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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]
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 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]
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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]
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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]
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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]
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