FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 338:1813-1821 June 18, 1998 Number 25 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text PDF Purchase this article Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Organ transplantation is now common. For patients with end-stage cardiac, hepatic, or pulmonary failure, it can be lifesaving.¹ For patients with diabetes mellitus, pancreatic transplantation offers the chance of a cure and the arrest or reversal of diabetic complications such as neuropathy and retinopathy. In 1996 more than 19,410 organ and tissue transplantations were performed in the United States, and 53,755 patients were on waiting lists for transplantation.

Over the past two decades, the development of new immunosuppressive drugs with improved efficacy and decreased toxicity has led to substantial improvement in the survival of patients and in short-term graft survival . . . [Full Text of this Article]

Role of T Cells in Transplant Rejection

Current Concepts in Immunosuppression

The Role of Costimulatory Signals in T-Cell Activation

T-Cell Costimulatory Blockade in Transplant Rejection

Acute Rejection

Chronic Rejection

Blockade of the CD40:CD40 Ligand Pathway

Preliminary Studies of Transplantation in Large Animals

Conclusions

Source Information

From the Laboratory of Immunogenetics and Transplantation, Renal Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston (M.H.S.); and the Department of Medicine, University of Pennsylvania, Philadelphia (L.A.T.).

Address reprint requests to Dr. Turka at the University of Pennsylvania, 901 Stellar Chance Laboratories, 422 Curie Blvd., Philadelphia, PA 19104-6100.

References

This article has been cited by other articles:

• Lobo, P. I., Schlegel, K. H., Spencer, C. E., Okusa, M. D., Chisholm, C., Mchedlishvili, N., Park, A., Christ, C., Burtner, C. (2008). Naturally Occurring IgM Anti-Leukocyte Autoantibodies (IgM-ALA) Inhibit T Cell Activation and Chemotaxis. J. Immunol. 180: 1780-1791 [Abstract] [Full Text]  
• Codarri, L., Vallotton, L., Ciuffreda, D., Venetz, J.-P., Garcia, M., Hadaya, K., Buhler, L., Rotman, S., Pascual, M., Pantaleo, G. (2007). Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7R{alpha}high cell population in solid organ transplant recipients. JEM 204: 1533-1541 [Abstract] [Full Text]  
• Sevigny, C. P., Li, L., Awad, A. S., Huang, L., McDuffie, M., Linden, J., Lobo, P. I., Okusa, M. D. (2007). Activation of Adenosine 2A Receptors Attenuates Allograft Rejection and Alloantigen Recognition. J. Immunol. 178: 4240-4249 [Abstract] [Full Text]  
• Cravedi, P., Noris, M., Remuzzi, G. (2007). Report of the First World Transplant Congress. CJASN 2: 393-400 [Abstract] [Full Text]  
• Najafian, N., Albin, M. J., Newell, K. A. (2006). How Can We Measure Immunologic Tolerance in Humans?. J. Am. Soc. Nephrol. 17: 2652-2663 [Abstract] [Full Text]  
• Salvalaggio, P. R. O., Camirand, G., Ariyan, C. E., Deng, S., Rogozinski, L., Basadonna, G. P., Rothstein, D. M. (2006). Antigen Exposure during Enhanced CTLA-4 Expression Promotes Allograft Tolerance In Vivo. J. Immunol. 176: 2292-2298 [Abstract] [Full Text]  
• Iacomini, J., Sayegh, M. H. (2006). Measuring T Cell Alloreactivity to Predict Kidney Transplant Outcomes: Are We There Yet?. J. Am. Soc. Nephrol. 17: 328-330 [Full Text]  
• Izawa, A., Sano, K., Takehara, M., Inobe, M., Suzuki, J.-i., Imamura, H., Takahashi, M., Ikeda, U., Isobe, M., Uede, T. (2006). Cre/loxP-mediated CTLA4IgG gene transfer induces clinically relevant immunosuppression via on-off gene recombination in vivo. Cardiovasc Res 69: 289-297 [Abstract] [Full Text]  
• Vincenti, F., Larsen, C., Durrbach, A., Wekerle, T., Nashan, B., Blancho, G., Lang, P., Grinyo, J., Halloran, P. F., Solez, K., Hagerty, D., Levy, E., Zhou, W., Natarajan, K., Charpentier, B., the Belatacept Study Group, (2005). Costimulation Blockade with Belatacept in Renal Transplantation. NEJM 353: 770-781 [Abstract] [Full Text]  
• El-Sawy, T., Belperio, J. A., Strieter, R. M., Remick, D. G., Fairchild, R. L. (2005). Inhibition of Polymorphonuclear Leukocyte-Mediated Graft Damage Synergizes With Short-Term Costimulatory Blockade to Prevent Cardiac Allograft Rejection. Circulation 112: 320-331 [Abstract] [Full Text]  
• Ito, T., Ueno, T., Clarkson, M. R., Yuan, X., Jurewicz, M. M., Yagita, H., Azuma, M., Sharpe, A. H., Auchincloss, H. Jr, Sayegh, M. H., Najafian, N. (2005). Analysis of the Role of Negative T Cell Costimulatory Pathways in CD4 and CD8 T Cell-Mediated Alloimmune Responses In Vivo. J. Immunol. 174: 6648-6656 [Abstract] [Full Text]  
• Sandner, S. E., Clarkson, M. R., Salama, A. D., Sanchez-Fueyo, A., Domenig, C., Habicht, A., Najafian, N., Yagita, H., Azuma, M., Turka, L. A., Sayegh, M. H. (2005). Role of the Programmed Death-1 Pathway in Regulation of Alloimmune Responses In Vivo. J. Immunol. 174: 3408-3415 [Abstract] [Full Text]  
• Yamada, A., Salama, A. D., Sho, M., Najafian, N., Ito, T., Forman, J. P., Kewalramani, R., Sandner, S., Harada, H., Clarkson, M. R., Mandelbrot, D. A., Sharpe, A. H., Oshima, H., Yagita, H., Chalasani, G., Lakkis, F. G., Auchincloss, H. Jr, Sayegh, M. H. (2005). CD70 Signaling Is Critical for CD28-Independent CD8+ T Cell-Mediated Alloimmune Responses In Vivo. J. Immunol. 174: 1357-1364 [Abstract] [Full Text]  
• Adams, A. B., Shirasugi, N., Jones, T. R., Durham, M. M., Strobert, E. A., Cowan, S., Rees, P., Hendrix, R., Price, K., Kenyon, N. S., Hagerty, D., Townsend, R., Hollenbaugh, D., Pearson, T. C., Larsen, C. P. (2005). Development of a Chimeric Anti-CD40 Monoclonal Antibody That Synergizes with LEA29Y to Prolong Islet Allograft Survival. J. Immunol. 174: 542-550 [Abstract] [Full Text]  
• Sayegh, M. H., Carpenter, C. B. (2004). Transplantation 50 Years Later -- Progress, Challenges, and Promises. NEJM 351: 2761-2766 [Full Text]  
• Doyle, A. M., Lechler, R. I., Turka, L. A. (2004). Organ Transplantation: Halfway through the First Century. J. Am. Soc. Nephrol. 15: 2965-2971 [Full Text]  
• Kotloff, R. M., Ahya, V. N., Crawford, S. W. (2004). Pulmonary Complications of Solid Organ and Hematopoietic Stem Cell Transplantation. Am. J. Respir. Crit. Care Med. 170: 22-48 [Abstract] [Full Text]  
• Dall'Era, M, Davis, J (2004). CTLA4Ig: a novel inhibitor of costimulation. Lupus 13: 372-376 [Abstract]  
• Mirenda, V., Berton, I., Read, J., Cook, T., Smith, J., Dorling, A., Lechler, R. I. (2004). Modified Dendritic Cells Coexpressing Self and Allogeneic Major Histocompatability Complex Molecules: An Efficient Way to Induce Indirect Pathway Regulation. J. Am. Soc. Nephrol. 15: 987-997 [Abstract] [Full Text]  
• Crompton, J. A. (2003). Transplant Immunology. Journal of Pharmacy Practice 16: 373-379 [Abstract]  
• Vassalli, G., Fleury, S., Li, J., Goy, J.-J., Kappenberger, L., von Segesser, L. K. (2003). Gene transfer of cytoprotective and immunomodulatory molecules for prevention of cardiac allograft rejection. Eur. J. Cardiothorac. Surg. 24: 794-806 [Abstract] [Full Text]  
• Soper, B. W., Lessard, M. D., Jude, C. D., Schuldt, A. J. T., Bunte, R. M., Barker, J. E. (2003). Successful Allogeneic Neonatal Bone Marrow Transplantation Devoid of Myeloablation Requires Costimulatory Blockade. J. Immunol. 171: 3270-3277 [Abstract] [Full Text]  
• Xu, J., Lucas, R., Schuchmann, M., Kuhnle, S., Meergans, T., Barreiros, A. P., Lohse, A. W., Otto, G., Wendel, A. (2003). GM-CSF Restores Innate, But Not Adaptive, Immune Responses in Glucocorticoid-Immunosuppressed Human Blood In Vitro. J. Immunol. 171: 938-947 [Abstract] [Full Text]  
• Vincenti, F. (2003). Immunosuppression Minimization: Current and Future Trends in Transplant Immunosuppression. J. Am. Soc. Nephrol. 14: 1940-1948 [Full Text]  
• Futamatsu, H., Suzuki, J.-i., Kosuge, H., Yokoseki, O., Kamada, M., Ito, H., Inobe, M., Isobe, M., Uede, T. (2003). Attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway. Cardiovasc Res 59: 95-104 [Abstract] [Full Text]  
• Salama, A. D., Najafian, N., Clarkson, M. R., Harmon, W. E., Sayegh, M. H. (2003). Regulatory CD25+ T Cells in Human Kidney Transplant Recipients. J. Am. Soc. Nephrol. 14: 1643-1651 [Abstract] [Full Text]  
• Watschinger, B., Pascual, M. (2002). Capillary C4d Deposition as a Marker of Humoral Immunity in Renal Allograft Rejection. J. Am. Soc. Nephrol. 13: 2420-2423 [Full Text]  
• Demirci, G., Gao, W., Zheng, X. X., Malek, T. R., Strom, T. B., Li, X. C. (2002). On CD28/CD40 Ligand Costimulation, Common {gamma}-Chain Signals, and the Alloimmune Response. J. Immunol. 168: 4382-4390 [Abstract] [Full Text]  
• Laskowski, I. A., Pratschke, J., Wilhelm, M. J., Dong, V. M., Beato, F., Taal, M., Gasser, M., Hancock, W. W., Sayegh, M. H., Tilney, N. L. (2002). Anti-CD28 Monoclonal Antibody Therapy Prevents Chronic Rejection of Renal Allografts in Rats. J. Am. Soc. Nephrol. 13: 519-527 [Abstract] [Full Text]  
• Yamada, A., Salama, A. D., Sayegh, M. H. (2002). The Role of Novel T Cell Costimulatory Pathways in Autoimmunity and Transplantation. J. Am. Soc. Nephrol. 13: 559-575 [Full Text]  
• Adams, A. B., Shirasugi, N., Durham, M. M., Strobert, E., Anderson, D., Rees, P., Cowan, S., Xu, H., Blinder, Y., Cheung, M., Hollenbaugh, D., Kenyon, N. S., Pearson, T. C., Larsen, C. P. (2002). Calcineurin Inhibitor-Free CD28 Blockade-Based Protocol Protects Allogeneic Islets in Nonhuman Primates. Diabetes 51: 265-270 [Abstract] [Full Text]  
• Najafian, N., Salama, A. D., Fedoseyeva, E. V., Benichou, G., Sayegh, M. H. (2002). Enzyme-Linked Immunosorbent Spot Assay Analysis of Peripheral Blood Lymphocyte Reactivity to Donor HLA-DR Peptides: Potential Novel Assay for Prediction of Outcomes for Renal Transplant Recipients. J. Am. Soc. Nephrol. 13: 252-259 [Abstract] [Full Text]  
• Yamada, A., Chandraker, A., Laufer, T. M., Gerth, A. J., Sayegh, M. H., Auchincloss, H. Jr. (2001). Cutting Edge: Recipient MHC Class II Expression Is Required to Achieve Long-Term Survival of Murine Cardiac Allografts After Costimulatory Blockade. J. Immunol. 167: 5522-5526 [Abstract] [Full Text]  
• Mandelbrot23, D. A., Kishimoto, K., Auchincloss, H. Jr., Sharpe, A. H., Sayegh, M. H. (2001). Rejection of Mouse Cardiac Allografts by Costimulation in trans. J. Immunol. 167: 1174-1178 [Abstract] [Full Text]  
• Hara, M., Kingsley, C. I., Niimi, M., Read, S., Turvey, S. E., Bushell, A. R., Morris, P. J., Powrie, F., Wood, K. J. (2001). IL-10 Is Required for Regulatory T Cells to Mediate Tolerance to Alloantigens In Vivo. J. Immunol. 166: 3789-3796 [Abstract] [Full Text]  
• Lee, R. S., Yamada, K., Houser, S. L., Womer, K. L., Maloney, M. E., Rose, H. S., Sayegh, M. H., Madsen, J. C. (2001). Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy. Proc. Natl. Acad. Sci. USA 98: 3276-3281 [Abstract] [Full Text]  
• Lee, R. S., Rusche, J. R., Maloney, M. E., Sachs, D. H., Sayegh, M. H., Madsen, J. C. (2001). CTLA4Ig-Induced Linked Regulation of Allogeneic T Cell Responses. J. Immunol. 166: 1572-1582 [Abstract] [Full Text]  
• Tzianabos, A. O., Chandraker, A., Kalka-Moll, W., Stingele, F., Dong, V. M., Finberg, R. W., Peach, R., Sayegh, M. H. (2000). Bacterial Pathogens Induce Abscess Formation by CD4+ T-Cell Activation via the CD28-B7-2 Costimulatory Pathway. Infect. Immun. 68: 6650-6655 [Abstract] [Full Text]  
• Melter, M., Reinders, M. E. J., Sho, M., Pal, S., Geehan, C., Denton, M. D., Mukhopadhyay, D., Briscoe, D. M. (2000). Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. Blood 96: 3801-3808 [Abstract] [Full Text]  
• Abrams, J. R., Kelley, S. L., Hayes, E., Kikuchi, T., Brown, M. J., Kang, S., Lebwohl, M. G., Guzzo, C. A., Jegasothy, B. V., Linsley, P. S., Krueger, J. G. (2000). Blockade of T Lymphocyte Costimulation with Cytotoxic T Lymphocyte-associated Antigen 4-Immunoglobulin (CTLA4Ig) Reverses the Cellular Pathology of Psoriatic Plaques, Including the Activation of Keratinocytes, Dendritic Cells, and Endothelial Cells. JEM 192: 681-694 [Abstract] [Full Text]  
• Mehling, A., Grabbe, S., Voskort, M., Schwarz, T., Luger, T. A., Beissert, S. (2000). Mycophenolate Mofetil Impairs the Maturation and Function of Murine Dendritic Cells. J. Immunol. 165: 2374-2381 [Abstract] [Full Text]  
• Gorczynski, R. M., Chen, Z., Clark, D. A., Hu, J., Yu, G., Li, X., Tsang, W., Hadidi, S. (2000). Regulation of Gene Expression of Murine MD-1 Regulates Subsequent T Cell Activation and Cytokine Production. J. Immunol. 165: 1925-1932 [Abstract] [Full Text]  
• Delves, P. J., Roitt, I. M. (2000). The Immune System- Second of Two Parts. NEJM 343: 108-117 [Full Text]  
• TOMASONI, S., AZZOLLINI, N., CASIRAGHI, F., CAPOGROSSI, M. C., REMUZZI, G., BENIGNI, A. (2000). CTLA4Ig Gene Transfer Prolongs Survival and Induces Donor-Specific Tolerance in a Rat Renal Allograft. J. Am. Soc. Nephrol. 11: 747-752 [Abstract] [Full Text]  
• Lee, R. S., Yamada, K., Womer, K. L., Pillsbury, E. P., Allison, K. S., Marolewski, A. E., Geng, D., Thall, A. D., Arn, J. S., Sachs, D. H., Sayegh, M. H., Madsen, J. C. (2000). Blockade of CD28-B7, But Not CD40-CD154, Prevents Costimulation of Allogeneic Porcine and Xenogeneic Human Anti-Porcine T Cell Responses. J. Immunol. 164: 3434-3444 [Abstract] [Full Text]  
• Guttormsen, H.-K., Sharpe, A. H., Chandraker, A. K., Brigtsen, A. K., Sayegh, M. H., Kasper, D. L. (1999). Cognate Stimulatory B-Cell-T-Cell Interactions Are Critical for T-Cell Help Recruited by Glycoconjugate Vaccines. Infect. Immun. 67: 6375-6384 [Abstract] [Full Text]  
• Dekel, B., Bocher, W. O., Marcus, H., Yussim, A., Reisner, Y. (1999). Acute cellular rejection of human renal tissue by adoptive transfer of allogeneic human peripheral blood mononuclear cells into chimeric rats: sequential gene expression of cytokines, chemokines and cytolytic effector molecules, and their regulation by CTLA-4-Ig. Int Immunol 11: 1673-1683 [Abstract] [Full Text]  
• Mandelbrot, D. A., Furukawa, Y., McAdam, A. J., Alexander, S. I., Libby, P., Mitchell, R. N., Sharpe, A. H. (1999). Expression of B7 Molecules in Recipient, Not Donor, Mice Determines the Survival of Cardiac Allografts. J. Immunol. 163: 3753-3757 [Abstract] [Full Text]  
• Harlan, D. M., Kirk, A. D. (1999). The Future of Organ and Tissue Transplantation: Can T-Cell Costimulatory Pathway Modifiers Revolutionize the Prevention of Graft Rejection?. JAMA 282: 1076-1082 [Abstract] [Full Text]  
• MURPHY, B., KRENSKY, A. M. (1999). HLA-Derived Peptides as Novel Immunomodulatory Therapeutics. J. Am. Soc. Nephrol. 10: 1346-1355 [Abstract] [Full Text]  
• GUDMUNDSDOTTIR, H., TURKA, L. A. (1999). T Cell Costimulatory Blockade: New Therapies for TransplantRejection. J. Am. Soc. Nephrol. 10: 1356-1365 [Abstract] [Full Text]  
• Zheng, X. X., Markees, T. G., Hancock, W. W., Li, Y., Greiner, D. L., Li, X. C., Mordes, J. P., Sayegh, M. H., Rossini, A. A., Strom, T. B. (1999). CTLA4 Signals Are Required to Optimally Induce Allograft Tolerance with Combined Donor-Specific Transfusion and Anti-CD154 Monoclonal Antibody Treatment. J. Immunol. 162: 4983-4990 [Abstract] [Full Text]  
• Arcasoy, S. M., Kotloff, R. M. (1999). Lung Transplantation. NEJM 340: 1081-1091 [Full Text]  
• Song, H. K., Noorchashm, H., Lieu, Y. K., Rostami, S., Greeley, S. A. S., Barker, C. F., Naji, A. (1999). Cutting Edge: Alloimmune Responses Against Major and Minor Histocompatibility Antigens: Distinct Division Kinetics and Requirement for CD28 Costimulation. J. Immunol. 162: 2467-2471 [Abstract] [Full Text]  
• Burlingham, W. J., Grailer, A. P., Heisey, D. M., Claas, F. H.J., Norman, D., Mohanakumar, T., Brennan, D. C., de Fijter, H., van Gelder, T., Pirsch, J. D., Sollinger, H. W., Bean, M. A. (1998). The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors. NEJM 339: 1657-1664 [Abstract] [Full Text]  
• Issazadeh, S., Navikas, V., Schaub, M., Sayegh, M., Khoury, S. (1998). Kinetics of Expression of Costimulatory Molecules and Their Ligands in Murine Relapsing Experimental Autoimmune Encephalomyelitis In Vivo. J. Immunol. 161: 1104-1112 [Abstract] [Full Text]  
• Ferri, C., Properzi, G., Tomassoni, G., Santucci, A., Desideri, G., Giuliani, A. E., Starling, R. C., Ratliff, N. B., Cook, D. J., McCarthy, P., Young, J. B., Yamani, M. H. (2002). Patterns of Myocardial Endothelin-1 Expression and Outcome After Cardiac Transplantation. Circulation 105: 1768-1771 [Abstract] [Full Text]