Advertisement

The Mechanisms and Significance of Apoptotic Cell-Mediated Immune Regulation

  • Erwei Sun
  • Yufang Shi
Chapter

Abstract

The discovery of apoptosis has prompted scientists in biology and medicine to explore the mechanisms and clinical significance of this fascinating phenomenon. In the last decade, accumulating evidence has revealed that apoptosis plays a pivotal role in almost every aspect of growth, differentiation and development. Although it is known that apoptotic cells are rapidly scavenged as a means to prevent inflammation, it remains to be determined whether the clearance of apoptotic cells is related to immune regulation. A review of the recent literature combined with our own work shows that apoptosis is not only a programmed and conserved process of cell death, but also exerts unique effects on the immune system, i.e. apoptotic cell-mediated immune regulation (AMIR). It seems that phagocytes, along with their cytokines released upon binding, phagocytosing and processing apoptotic cells, lie at the heart of AMIR. Investigation of AMIR will not only bring about a better understanding of many important physiological and pathological mechanisms, but also provide new hope for patients of transplantation and autoimmune diseases.

Keywords

Systemic Lupus Erythematosus Apoptotic Cell Systemic Lupus Erythematosus Patient Kupffer Cell Immune Tolerance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Albert, M. L., Pearce, F. A., Francisco, L. M., Sauter, B., Roy, P., Silverstein, R. L., and Bhardwaj, N. (1998a). Immature dendritic cells phagocytose apoptotic cells via alpha-v-beta-s and CD36, and cross-pressent antigens to cytotoxic T lymphocytes. J Exp Med 188: 1359–1368.PubMedCrossRefGoogle Scholar
  2. Albert, M. L., Saiter, B., and Bhardwaj, N. (1998b). Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392: 86–89.PubMedCrossRefGoogle Scholar
  3. Andrade, F., Casciola-Rosen, L., and Rosen, A. (2000). Apoptosis in systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am 26:215–27, v.Google Scholar
  4. Barrington, R., Zhang, M., Fischer, M., and Carroll, M. C. (2001). The role of complement in inflammation and adaptive immunity. Immunol Rev 180: 5–15.PubMedCrossRefGoogle Scholar
  5. Belz, G. T., Altman, J. D., and Doherty, P. C. (1998). Characteristics of virus-specific CD8+ T cells in the liverGoogle Scholar
  6. during the control and resolution phases of influenza pneumonia Proc Natl Acad Sci USA 95:13812–13817.Google Scholar
  7. Bissell, D. M., Roulot, D., and George, J. (2001). Transforming growth factor beta and the liver. Hepatology 34: 859–867.PubMedCrossRefGoogle Scholar
  8. Bissell, D. M., Wang, S. S., Jarnagin, W. R., and Roll, F. J. (1995). Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation. J Clin Invest 96: 447–455.PubMedCrossRefGoogle Scholar
  9. Boeckx, W., Sobis, H., Lacquet, A., Gruwez, J., and Vandeputte, M. (1975). Prolongation of allogeneic heart graft survival in the rat after implantation on portal vein. Transplantation 19: 145–149.PubMedCrossRefGoogle Scholar
  10. Botto, M. (1998). Clq knock-out mice for the study of complement deficiency in autoimmune disease. Exp Clin Immunogenet 15: 231–234.PubMedCrossRefGoogle Scholar
  11. Botto, M., Dell’Agnola, C., Bygrave, A. E., Thompson, E. M., Cook, H. T., Petry, F., Loos, M., Pandolfi, P. P., and Walport, M. J. (1998). Homozygous Clq deficiency causes glomerulonephritis associated with multiple apoptotic bodies [see comments]. Nat Genet 19: 56–59.PubMedCrossRefGoogle Scholar
  12. Bumgardner, G. L., Gao, D., Li, J., Baskin, J. H., Heininger, M., and Orosz, C. G. (2000). Rejection responses to allogeneic hepatocytes by reconstituted SCID mice, CD4, KO, and CD8 KO mice. Transplantation 70: 1771–1780.PubMedCrossRefGoogle Scholar
  13. Bumgardner, G. L., Li, J., Heininger, M., Ferguson, R. M., and Orosz, C. G. (1998). In vivo immunogenicity of purified allogeneic hepatocytes in a murine hepatocyte transplant model. Transplantation 65: 47–52.PubMedCrossRefGoogle Scholar
  14. Bumgardner, G. L., Li, J., Prologo, J. D., Heininger, M., and Orosz, C. G. (1999). Patterns of immune responses evoked by allogeneic hepatocytes: evidence for independent co-dominant roles for CD4+ and CD8+ T-cell responses in acute rejection. Transplantation 68: 555–562.PubMedCrossRefGoogle Scholar
  15. Bumgardner, G. L., and Orosz, C. G. (2000). Unusual patterns of alloimmunity evoked by allogeneic liver parenchymal cells. Immunol Rev 174: 260–279.PubMedCrossRefGoogle Scholar
  16. Callery, M. R, Kamei, T., and Flye, M. W. (1989a). The effect of portacaval shunt on delayed-hypersensitivity responses following antigen feeding. J Surg Res 46: 391–394.PubMedCrossRefGoogle Scholar
  17. Callery, M. P., Kamei, T., and Flye, M. W. (1989b). Kupffer cell blockade inhibits induction of tolerance by the portal venous route. Transplantation 47: 1092–1094.PubMedCrossRefGoogle Scholar
  18. Casciola-Roen, L. A., Anhalt, G., and Rosen, A. (2000). Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 179: 1317–1330.CrossRefGoogle Scholar
  19. Cella, M., Engering, A., Pinet, V., Pieters, J., and Lanzavecchia, A. (1997). Inflammatory stimuli induce accumu-lation of MHC class II complexes on dendritic cells [see comments]. Nature 388: 782–7.PubMedCrossRefGoogle Scholar
  20. Chen, W.-J., Frank, M. E., Jin, W., and Wahl, S. M. (2001). TGF-Released by Apoptotic T Cells Contributes to an Immunosuppressive Milieu. Immunity 14: 715–725.PubMedCrossRefGoogle Scholar
  21. Cousens, L. P., and Wing, E. J. (2000). Innate defenses in the liver during Listeria infection. Immunol Rev 174: 150–159.PubMedCrossRefGoogle Scholar
  22. Crispe, I. N., Dao, T., Klugewitz, K., Mehal, W. Z., and Metz, D. P. (2000). The liver as a site of T-cell apoptosis: graveyard, or killing field? Immunol Rev 174: 47–62.PubMedCrossRefGoogle Scholar
  23. Devitt, A., Moffatto, O., Raykundalia, C., Capra, J. D., Simmons, D. L., and Gregory, C. D. (1998). Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 392: 505–509.PubMedCrossRefGoogle Scholar
  24. Dini, L., and Carla, E. C. (1998). Hepatic sinusoidal endothelium heterogeneity with respect to the recognition of apoptotic cells. Exp Cell Res 240: 388–393.PubMedCrossRefGoogle Scholar
  25. Doherty, D. G., Norris, S., Madrigal-Estebas, L., McEntee, G., Traynor, O., Hegarty, J. E., and O’Farrelly, C. (1999). The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Thl, Th2, and Th0 cytokine secretion patterns. J Immunol 163: 2314–2321.PubMedGoogle Scholar
  26. Fadok, V. A., Bratton, D. L., Freed, P. W., Westcott, J. Y., and P. M., H. (1998). Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2 AND PAF. J Clin Invest 101: 890–898.PubMedCrossRefGoogle Scholar
  27. Fadok, V. A., Bratton, D. L., Rose, D. M., Pearson, A., Ezekewitz, R. A., and Henson, P. M. (2000). A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405: 85–90.PubMedCrossRefGoogle Scholar
  28. Fecteau, A., Tchervenkow, J., Guttman, F., Takara, T., and Rosenmann, E. (1994). Small bowel transplantation: the effects of intraportal donor-specific transfusion 24 hours pretransplant and low-sose cyclosporine. Transplantation 58: 399–402.PubMedCrossRefGoogle Scholar
  29. Feng, H., Zeng, Y., Whitesell, L., and Katsanis, E. (2001). Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity. Blood 97: 3505–3512.PubMedCrossRefGoogle Scholar
  30. Ferguson, T. A., and Griffith, T. S. (1997). A vision of cell death: insights into immune privilege. Immunol Rev 156: 167–184.PubMedCrossRefGoogle Scholar
  31. Frabetti, F., Tazzari, P. L., Musiani, D., Bontadini, A., Matteini, C., Roseti, L., Tassi, C., Viggiani, M., Marini, M., and Conte, R. (2000). White cell apoptosis in platelet concentrates. Transfusion 40: 160–168.PubMedCrossRefGoogle Scholar
  32. Gagne, K., Brouard, S., Guillet, M., Cuturi, M. C., and Souilillou, J. P. (2001). TGF-betal and donor dendritic cells are common key components in donor-specific blood transfusion and anti-class II heart graft enhancement, whereas tolerance induction also required inflammatory cytokines down-regulation. Eur J Immunol 31: 3111–3120.PubMedCrossRefGoogle Scholar
  33. Gershov, D., Kim, S., Brot, N., and Elkon, K. B. (2000). C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 192: 1353–1364.PubMedCrossRefGoogle Scholar
  34. Gorczynski, R. M., Chan, Z., Chung, S., Cohen, Z., Levy, G., sullivan, B., and Fu, X. M. (1994). Prolongation of rat small bowel or renal allograft survival by pretransplant transfusion and/or by varying the route of allograft venous drainage. Transplantation 58: 816–820.PubMedGoogle Scholar
  35. Gorczynski, R. M., Fu, X. M., Church, D. J., sullivan, B., and Chen, Z. (1995). Manipulation of xenogeneic skin and/or renal graft survival in the rat-mouse concordant combination by portal vein pretransplantation transfusion. Transplant Immunol 3: 321–329.CrossRefGoogle Scholar
  36. Goss, J. A., Flye, M. W., and Lacy, P. E. (1996). Induction of allogeneic islet survival by intrahepatic islet pre-immunization and transient immunosuppression. Diabetes 45: 144–147.PubMedCrossRefGoogle Scholar
  37. Griffith, T. S., Yu, X., Herndon, J. M., Green, D. R., and T. A., F. (1996). CD95-induced apoptosis of lymphocytes in an immune privileged site induces immunological tolerance. Immunity 5: 7–16.PubMedCrossRefGoogle Scholar
  38. Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M., Ravetch, J. V., Steinman, R. M., and Nussenzweig, M. C. (2001). Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194: 769–79.PubMedCrossRefGoogle Scholar
  39. Hengartner, M. O. (2001). Apoptosis: corralling the corpses. Cell 104: 325–328.PubMedCrossRefGoogle Scholar
  40. Huang, F.-P., Platta, N., Wykesa, M., Majora, J. R., Powella, T. J., Jenkinsa, C. D., and MacPhersona, G. G. (2000). A Discrete Subpopulation of Dendritic Cells Transports Apoptotic Intestinal Epithelial Cells to T Cell Areas of Mesenteric Lymph Nodes. J Exp Med 191: 435–444.PubMedCrossRefGoogle Scholar
  41. Huang, L., Soldevila, G., Leeker, M., Flavell, R., and Crispe, I. N. (1994). The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo. Immunity 1: 741–749.PubMedCrossRefGoogle Scholar
  42. Huynh, M. L., Fadok, V. A., and Henson, P. M. (2002). Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-betal secretion and the resolution of inflammation. J Clin Invest 109: 41–50.PubMedGoogle Scholar
  43. Inaba, K., Turley, S., Iyoda, T., Yamaide, F., Shimoyama, S., Reis e Sousa, C., Germain, R. N., Mellman, I., and Steinman, R. M. (2000). The Formation of Immunogenic Major Histocompatibility Complex Class IIC Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli. J Exp Med 191: 927–936.PubMedCrossRefGoogle Scholar
  44. Josien, R., Douillard, P., Guillot, C., Muschen, M., Anegon, I., Chetritt, J., Menoret, S., Vignes, C., Soulillou, J. P., and Cuturi, M. C. (1998). A critical role for transforming growth factor-beta in donor transfusion-induced allograft tolerance. J Clin Invest 102: 1920–1926.PubMedCrossRefGoogle Scholar
  45. Kamada, N., Davies, H. F. S., and Roser, B. (1981). Reversal of transplantation immunity by liver grafting. Nature 292: 840–842.PubMedCrossRefGoogle Scholar
  46. Kamada, N., Teramoto, K., Baguerizo, A., Ishikawa, M., Suminoto, R., and Ohkouchi, Y. (1998). Cellular basis of transplantation tolerance induced by liver grafting in the rat. Transplantation 46: 165–167.CrossRefGoogle Scholar
  47. Kamei, T., Callery, M. P., and Flye, M. W. (1990). Kupffer cell blockade prevents induction of portal venous tolerance n rat cardiac allograft transplantation. J Surg Res 48: 393–396.PubMedCrossRefGoogle Scholar
  48. Kishore, U., and Reid, K. B. (2000). Clq: structure, function, and receptors. Immunopharmacology 49: 159–170.PubMedCrossRefGoogle Scholar
  49. Knolle, P., Schlaak, J., Uhrig, A., Kempf, P., Meyer zum Buschenfelde, K. H., and Gerken, G. (1995). Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J Hepatol 22: 226–229.PubMedCrossRefGoogle Scholar
  50. Knolle, P. A., Germann, T., Treichel, U., Uhrig, A., Schmitt, E., Hegenbarth, S., Lohse, A. W., and Gerken, G. (1999). Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells. J Immunol 162: 1401–1407.PubMedGoogle Scholar
  51. Korb, L. C., and Ahearn, J. M. (1997). Clq binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J Immunol 158: 4525–4528.PubMedGoogle Scholar
  52. Lorenz, H. M., Herrmann, M., Winkler, T., Gaipl, U., and Kalden, J. R. (2000). Role of apoptosis in autoimmunity. Apoptosis 5: 443–449.PubMedCrossRefGoogle Scholar
  53. Luan, J. J., Monteiro, R. C., Sautes, C., Fluteau, G., Eloy, L., Fridman, W. H., Bach, J. F., and Garchon, H. J. (1996). Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum. J Immunol 157: 4707–4716.PubMedGoogle Scholar
  54. Lumsden, A. B., Henderson, J. M., and Kutner, M. H. (1988). Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis. Hepatology 8: 232–236.PubMedCrossRefGoogle Scholar
  55. Markees, T. G., Serreze, D. V., Phillips, N. E., Sorli, C. H., Gordon, E. J., Shultz, L. D., Noelle, R. J., Woda, B. A., Greiner, D. L., Mordes, J. P., and Rossini, A. A. (1999). NOD mice have a generalized defect in their response to transplantation tolerance induction. Diabetes 48: 967–74.PubMedCrossRefGoogle Scholar
  56. Mehal, W. Z., Juedes, A. E., and Crispe, I. N. (1999). Selective retention of activated CD8+ T cells by the normal liver. J Immunol 163: 3202–3210.PubMedGoogle Scholar
  57. Mevorach, D., Mascarenhas, J. O., Gershov, D., and Elkon, K. B. (1998). Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 188: 2313–2320.PubMedCrossRefGoogle Scholar
  58. Morita, H., Sugiura, K., Inaba, M., Jin, T., Ishikawa, J., Lian, Z., Adachi, Y., Sogo, S., Yamanishi, K., Taki, H., et al. (1998). A strategy for organ allografts without using immunosuppressants or irrdiation. Proc Natl Acad Sci USA 95: 6947–6952.PubMedCrossRefGoogle Scholar
  59. Muschen, M., Warskulat, U., Douillard, P., Gilbert, E., and Haussinger, D. (1998). Regulation of CD95 (APO-1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells. Hepatology 27: 200–208.PubMedCrossRefGoogle Scholar
  60. Muschen, M., Warskulat, U., Peters, R. T., Bode, J. G., Kubitz, R., and Haussinger, D. (1999). Involvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation. Gastroenterology 116: 666–677.PubMedCrossRefGoogle Scholar
  61. Nakano, Y., Monden, M., Valdevia, L. A., Gotoh, M., Tono, T., and Mori, T. (1992). Permanent acceptance of liver allografs by intraportal injection of donor spleen cells in rats. Surgery 111: 668–676.PubMedGoogle Scholar
  62. Navratil, J. S., Korb, L. C., and Ahearn, J. M. (1999). Systemic lupus erythematosus and complement deficiency: clues to a novel role for the classical complement pathway in the maintenance of immune tolerance. Immunopharmacology 42: 47–52.PubMedCrossRefGoogle Scholar
  63. Nielsen, H. J. (1995). Detrimental effects of perioperative blood transfusion. Br J Surg 82: 582–587.PubMedCrossRefGoogle Scholar
  64. Opelz, G., and Terasaki, P. I. (1974). Poor kidney-transplant survival in recipients with frozen-blood transfusions or no transfusions. Lancet 2: 696–698.PubMedCrossRefGoogle Scholar
  65. Persijn, G. G., Cohen, B., Lansbergen, Q., and Van Rood, J. J. (1979). Retrospective and prospective studies on the effect of blood transfusions in renal transplantation in The Netherlands. Transplantation 28: 396–401.PubMedCrossRefGoogle Scholar
  66. Platt, N., Suzuki, H., Kurihara, Y., Kodama, T., and Gordon, S. (1996). Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc Natl Acad Sci USA 93: 12456–12460.PubMedCrossRefGoogle Scholar
  67. Ponner, B. B., Stach, C., Zoller, O., Hagenhofer, M., Voll, R. E., Kalden, J. R., and Herrmann, M. (1998). Induction of apoptosis reduces immunogenicity of human T-cell lines in mice. Scand J Immunol 47: 343–347.PubMedCrossRefGoogle Scholar
  68. Rabinovitch, A., Suarez-Pinzon, W. L., Shi, Y., Morgan, A. R., Bleackley, R. C. DNA fragmentation is an early event in cytokine-induced islet beta-cell destruction. Diabetologia 1994 Aug; 37: 733–738.PubMedCrossRefGoogle Scholar
  69. Riordan, S. M., and Williams, R. (1999). Tolerance after liver transplantation: does it exist and can immunosup-pression be withdrawn? J Hepatol 31: 1106–1119.PubMedCrossRefGoogle Scholar
  70. Rodenburg, R. J., Raats, J. M., Pruijn, G. J., and van Venrooij, W. J. (2000). Cell death: a trigger of autoimmunity? Bioessays 22: 627–636.PubMedCrossRefGoogle Scholar
  71. Rovere, P., Sabbadini, M. G., Fazzini, F., Bondanza, A., Zimmermann, V. S., Rugarli, C., and Manfredi, A. A. (2000). Remnants of suicidal cells fostering systemic autoaggression. Apoptosis in the origin and maintenance of autoimmunity. Arthritis Rheum 43: 1663–1672.PubMedCrossRefGoogle Scholar
  72. Rovere, P., Sabbadini, M. G., Vallinoto, C., Fascio, U., Recigno, M., Crosti, M., Ricciardi-Castagnoli, R, Balestrieri, G., Tincani, A., and Manfredi, A. A. (1999). Dendritic cell presentation of antigens from apoptotic cells in a proinflammatory context: role of opsonizing anti-beta2-glycoprotein I antibodies. Arthritis Rheum 42: 1412–1420.PubMedCrossRefGoogle Scholar
  73. Rovere, P., Vallinoto, C., Bondanza, A., Crosti, M. C., Rescigno, M., Ricciardi-Castagnoli, P., Rugarli, C., and Manfredi, A. A. (1998). Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J Immunol 161: 4467–4471.PubMedGoogle Scholar
  74. Sauter, B., Albert, M. L., Francisco, L., Larsson, M., Somersan, S., and Bhardwaj, N. (2000). Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells [see comments]. J Exp Med 191: 423–434.PubMedCrossRefGoogle Scholar
  75. Savill, J. (1998). Apoptosis. Phagocytic docking without shocking [news; comment]. Nature 392: 442–443.PubMedCrossRefGoogle Scholar
  76. Savill, J., and Fadok, V. (2000). Corpse clearance defines the meaning of cell death Nature 407: 784–788.Google Scholar
  77. Scitt, r. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S., and Matsisjoma, G. K. (2001). Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 410: 207.CrossRefGoogle Scholar
  78. Seki, S., Habu, Y., Kawamura, T., Takeda, K., Dobashi, H., Ohkawa, T., and Hiraide, H. (2000). The liver as a crucial organ in the first line of host defense:the roles fo Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper I immune response. Immunol Rev 174: 35–46.PubMedCrossRefGoogle Scholar
  79. Serreze, D. V., Gaskins, H. R., and Leiter, E. H. (1993). Defects in the differentiation and function of antigen presenting cells in NOD/Lt mice. J Immunol 150: 2534–2543.PubMedGoogle Scholar
  80. Shi, Y., Zheng, W., and Rock, K. L. (2000). Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses. Proc Natl Acad Sci USA 97: 14590–14595.PubMedCrossRefGoogle Scholar
  81. Shi, Y. F., Sahai, B. M., and Green, D. R. (1989). Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes. Nature 339: 625–626.PubMedCrossRefGoogle Scholar
  82. Snyder, E. L., and Kuter, D. J. (2000). Apoptosis in transfusion medicine: of death and dying-is that all there is? [editorial; comment]. Transfusion 40: 135–138.PubMedCrossRefGoogle Scholar
  83. Starzl, T. E., Demetris, A. J., Murase, N., Trucco, M., Thomson, A. W., and Rao, A. S. (1996). The lost chord; microchimerism and allograft survival. Immunol Today 17: 577–584.PubMedCrossRefGoogle Scholar
  84. Starzl, T. E., Demetris, A. J., Mursase, N., Ildstad, S., Ricordi, C., and Trucco, M. (1992). Cell migration, chimerism and graft tolerance. Lancet 339: 1579.PubMedCrossRefGoogle Scholar
  85. simmunity and tolerance. N Engl J Med 339:1905–13.Google Scholar
  86. Steinman, R. M., Turley, S., Mellman, I., and Inaba, K. (2000). The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med 191: 411–416.PubMedCrossRefGoogle Scholar
  87. Sun, E., Zhang, L., Zeng, Y., Ge, Q., Zhao, M., and Gao, W. (2000). Apoptotic cells actively inhibit the expression of CD69 on con A activated T lymphocytes. Scand J Immunol 51: 231–236.PubMedCrossRefGoogle Scholar
  88. Sun, E., and Shi, Y. (2001). Apoptosis: the quiet death silences the immune system. Pharmacol Ther 92: 135–145.PubMedCrossRefGoogle Scholar
  89. Taylor, R. R., Carugati, A., Fadok, V. A., Cook, H. T., Andrew, M., Carroll, M. C., Savill, J. S., Henson, P. M., Botto, M., and Walport, M. J. (2000). A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 192: 359–366.PubMedCrossRefGoogle Scholar
  90. Thompson, C. B. (1995). Apoptosis in the pathogenesis and treatment of disease. Science 267: 1456–1462.PubMedCrossRefGoogle Scholar
  91. Thomson, A. W., and Lu, L. (1999). Are dendritic cells the key to liver transplant tolerance? Immunology Today 20: 27–32.PubMedCrossRefGoogle Scholar
  92. Tough, T. E., Sun, S., and Sprent, J. (1997). T cell stimulation in vivo by lipopolysaccharide (LPS). J Exp Med 185: 2089–2094.PubMedCrossRefGoogle Scholar
  93. Trudeau, J. D., Dutz, J. P., Arany, E., Hill, D. J., Fieldus, W. E., and Finegood, D. T. (2000). Neonatal beta-cell apoptosis: a trigger for autoimmune diabetes? Diabetes 49: 1–7.PubMedCrossRefGoogle Scholar
  94. Voll, R. E., Herrmann, M., Roth, E. A., Stach, C., and Kalden, J. (1997). Immunosuppressive effects of apoptotic cells. Nature 390: 350–351.PubMedCrossRefGoogle Scholar
  95. Well, A. D., Li, X. C., Li, Y., Walsh, M. C., Zhang, X. X., Wu, Z., Nunez, G., Tang, A., Sayegh, M., Hancock, W. W., et al. (1999). Requirement for T cell apoptosis in the induction of peripheral transplantation tolerance. Nat Med 5: 1303–1307.CrossRefGoogle Scholar
  96. Wood, K., and Sachs, D. H. (1996). Chimerism and transplantation tolerance: cause and effect. Immunol Today 17: 584–589.PubMedCrossRefGoogle Scholar
  97. Yang, R., Liu, Q., Grosfeld, J. L., and Pescovitz, M. D. (1994). Intestinal venous drainage through the liver is a prerequistite for oral tolerance induction. J Pediatr Surg 29: 1145–1148.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  1. 1.Organ Transplantation DepartmentZhujiang HospitalGuangzhouChina
  2. 2.Molecular Genetics, Microbiology and ImmunologyUniversity of Medicine and Dentistry of New JerseyPiscatawayUSA

Personalised recommendations