Molecular targets for genetic engineering in pig-to-human vascularized xenotransplantation

  • Bernard Vanhove
  • Jean-Paul Soulillou
Part of the Transplantation and Clinical Immunology book series (TRAC, volume 29)


Over the past few years, our understanding of the mechanisms involved in the rejection of discordant xenografts has greatly increased. Several molecules potentially involved in the rejection process have been identified, and the way in which they mediate their pathologic effect largely elucidated. At the same time, improvements in the technology of transgenesis in the pig have made it possible to produce donor animals expressing some of these molecules, particularly on endothelial cells, so that their actual role in the process of pig-to-primate xenograft rejection can be evaluated. One factor limiting genetic manipulation in pigs, however, is that the embryonic stem cells necessary for homologous recombination are currently unavailable, which makes it impossible to knock out a gene in that species. Emerging techniques such as intrabody-mediated phenotypic knockout, overexpression of dominant negative mutants, anti-sense RNA or ribozymes may represent alternatives and result in the production of donor animals with reduced expression of factors that initiate rejection. It is our assumption that combined expression of several protective transgenes associated with reduced expression of some of the endogenous proteins that promote rejection will make it possible to maintain a pig organ in the human body.


Tissue Factor Pathway Inhibitor Hyperacute Rejection Porcine Endothelial Cell Delay Xenograft Rejection Discordant Xenograft 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Parker W, Saadi S, Lin SS, Holzknecht ZE, Bustos M, Platt JL. Transplantation of discordant xenografts: a challenge revisited. Immunol. Today 1996; 17(8): 373–378.PubMedCrossRefGoogle Scholar
  2. 2.
    Bach FH, Winkler H, Ferran C, Hancock WW, Robson SC. Delayed xenograft rejection. Immunol. Today 1996; 17(8): 379–384.PubMedCrossRefGoogle Scholar
  3. 3.
    Dorling A, Riesbeck K, Lechler RI. The T-cell response to xenografts: molecular interactions and graft-specific immunosuppression. Xeno. 1996; 4(4): 68–76.Google Scholar
  4. 4.
    Bouhours D, Pourcel C, Bouhours JF. Simultaneous expression by porcine aorta endothelial cells of glycolipids bearing the major epitope for human xenoreactive antibodies (Galalpha1-3Gal), blood group H determinant and N-glycolylneuraminic acid. Glycoconjugate J. 1996; 13: 947–953.CrossRefGoogle Scholar
  5. 5.
    Parker W, Bruno D, Holzknecht ZE, Platt JL. Characterization and affinity isolation of xenoreactive human natural antibodies. J. Immunol. 1994; 153: 3791–3803.PubMedGoogle Scholar
  6. 6.
    Thibaudeau K, Borche L, Soulillou JP, Blanchard D. Characterization of porcine platelet glycoproteins recognized by human natural ‘anti-gal’ antibodies. Blood 1996; 87(11): 4636–4642.PubMedGoogle Scholar
  7. 7.
    Mirenda V, LeMauff B, Cassard A, Huvelin JM, Boeffard F, Faivre A, Soulillou JP, Anegon I. Intact pig pancreatic islet function in the presence of human xenonatural antibody binding and comlement activation. Transplantation 1997; in press.Google Scholar
  8. 8.
    Azimzadeh A, Wolf P, Dalmasso A, Odeh M, Beller JP, Fabre M, Charreau B, Thibeaudeau K, Cinqalbre J, Soulillou JP, Anegon I. Assessment of hyperacute rejection in a rat-to-primate cardiac xenograft model. Transplantation 1996; 61: 1305–1313.PubMedCrossRefGoogle Scholar
  9. 9.
    Saadi S, Platt JL. Transient perturbation of endothelial integrity induced by natural antibodies and complement. J. Exp. Med. 1995; 181: 21–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Platt JL, Vercellotti GM, Lindman BJ, Oegema TR, Bach FH, Dalmasso AP. Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection. J. Exp. Med. 1990; 171: 1363–1368.PubMedCrossRefGoogle Scholar
  11. 11.
    Jurd KM, Gibbs RV, Hunt BJ. Activation of human prothrombin by porcine aortic endothelial cells: a potential barrier to pig to human xenotransplantation. Blood Coagul. Fibrinolysis 1996; 7(3): 336–343.PubMedCrossRefGoogle Scholar
  12. 12.
    Robson SC, Kaczmarek E, Siegel JB, Candidas D, Koziak K, Millan M, Hancock WW, Bach FH. Loss of ATP diphosphohydrolase activity with endothelial cell activation. J. Exp. Med. 1997; 185(1): 153–163.PubMedCrossRefGoogle Scholar
  13. 13.
    Dalmasso AP, Vercellotti GM, Platt JL, Bach FH. Inhibition of complement-mediated endothelial cell cytotoxicity by decay-accelerating factor. Transplantation 1991; 52(3): 530–533.PubMedCrossRefGoogle Scholar
  14. 14.
    Bach FH, Robson SC, Winkler H, Ferran C, Stuhlmeier KM, Wrighton CJ, Hancock WW. Barriers to xenotransplantation. Nature Medicine 1995; 1(9): 869–873.PubMedCrossRefGoogle Scholar
  15. 15.
    Peerschke EIB, Reid KBM, Ghebrehiwet B. Platelet activation by Clq results in the induction of aIIb/B3 integrins (GPIIb-IIIa) and the expression of P-selection and procoagulant activity. J. Exp. Med. 1993; 178: 579–587.PubMedCrossRefGoogle Scholar
  16. 16.
    Vanhove B, Martin Rd, Lipp J, Bach FH. Human xenoreactive natural antibodies of the IgM isotype activate pig endothelial cells. Xenotransplantation 1994; 1: 17–23.Google Scholar
  17. 17.
    Sandrin MS, Fodor WL, Mouhtouris E, Osman N, Cohney S, Rollins SA, Guilmette ER, Setter E, Squinto SP, McKenzie IFC. Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substancially reduces human antibody binding and complement-mediated cytolysis. Nature Medicine 1995; 1(12): 1261–1266.PubMedCrossRefGoogle Scholar
  18. 18.
    Sharma A, Okabe J, Birch P, McCellan SB, Martin MJ, Platt JL, Logan JS. Reduction in the level of Gal(alpha1,3)Gal in transgenic mice and pigs by the expression of an alpha(1,2)fucosyltransferase. Proc. Natl. Acad. Sci. USA 1996; 93: 7190–7195.PubMedCrossRefGoogle Scholar
  19. 19.
    Hirafuji M, Mencia-Huerta JM, Benveniste J. Regulation of PAF-acether (platelet-activating factor) biosynthesis in cultured human vascular endothelial cells stimulated with thrombin. Biochim. Biophys. Acta 1987; 930: 359–369.PubMedCrossRefGoogle Scholar
  20. 20.
    Kroshus TJ, Rollins SA, Dalmasso AP, Elliott EA, Matis LA, Squinto SP, R.M. Bolman I. Complement inhibition with an anti-C5 monoclonal antibody prevents acute cardiac tissus injury in an ex vivo model of pig-to-human xenotransplantation. Transplantation 1995; 60(11): 1194–1202.PubMedGoogle Scholar
  21. 21.
    Rollins SA, Matis LA, Springhorn JP, Setter E, Wolf DW. Monoclonal antibodies directed against human C5 and C8 block complement-mediated damage of xenogenic cells and organs. Transplantation 1995; 60(11): 1284–1292.PubMedGoogle Scholar
  22. 22.
    Warner SJ, Auger KR, Libby P. Interleukin 1 induces interleukin 1. II. Recombinant human interleukin 1 induces interleukin 1 production by adult human vascular endothelial cells. J. Immunol. 1987; 139(6): 1911–1917.PubMedGoogle Scholar
  23. 23.
    Goodman DJ, vonAlbertini M, Willson A, Millan M, Bach FH. Direct activation of porcine endothelial cells by human natural killer cells. Transplantation 1995; 61(5): 763–771.CrossRefGoogle Scholar
  24. 24.
    Kopp CW, Siegel JB, Hancock WW, Anrather J, Winkler H, Geczy CL, Kaczmarek E, Bach FH, Robson SC. Effect of porcine endothelial tissue factor pathway inhibitor on human coagulation factors. Transplantation 1997; 63(5): 749–758.PubMedCrossRefGoogle Scholar
  25. 25.
    Emeis JJ, Kooistra T. Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J. Exp. Med. 1986; 163: 1260–1266.PubMedCrossRefGoogle Scholar
  26. 26.
    Nachman RL, Hajjar KA, Silverstein RL, Dinarello CA. Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor. J. Exp. Med. 1986; 163(6): 1595–1600.PubMedCrossRefGoogle Scholar
  27. 27.
    Conway EM, Bach R, Rosenberg RD, Koningsberg WH. Tumor necrosis factor enhances expression of tissue factor mRNA in endothelial cells. Throm. Res. 1989; 53(3): 231–241.CrossRefGoogle Scholar
  28. 28.
    Ripoche J, Mitchell JA, Erdei A, Madin C, Moffatt B, Mokoena T, Gordon S, Sim RB. Interferon gamma induces synthesis of complement alternative pathway proteins by humlan endothelial cells in culture. J. Exp. Med. 1988; 168(5): 1917–1922.PubMedCrossRefGoogle Scholar
  29. 29.
    Yoshizumi M, Kurihara H, Morita T, Yamashita T, Oh-hashi Y, Sugiyama T, Takaku F, Yanagisawa M, Masaki T, Yazaki Y. Interleukin 1 increases the production of endothelin-1 by cultured endothelial cells. Biochem. Biophys. Res. Commun. 1990; 166(1): 324–329.PubMedCrossRefGoogle Scholar
  30. 30.
    Gross SS, Jaffe EA, Levi R, Kilbourn RG. Cytokine-activated endothelial cells express an isotype of nitric oxide synthase which is tetrahydrobiopterin-dependant, calmodulin-independant and inhibited by arginine analogs with a rank-order of potency characteristic of activated macrophages. Biochem. Biophys. Res. Commun. 1991; 178(3): 823–829.PubMedCrossRefGoogle Scholar
  31. 31.
    Sica A, Matsushima K, VanDamma J, Wang JM, Polentarutti N, Dejena E, Colotta F, Mantovani A. IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells. Immunology 1990; 69(4): 548–553.PubMedGoogle Scholar
  32. 32.
    deMartin R, Vanhove B, Cheng Q, Hofer E, Czismadia V, Winkler H, Bach FH. Cytokine-inducible expression in entothelial cells of an IκBa-like gene is regulated by NFκB. EMBO J. 1993; 7: 2773–2779.Google Scholar
  33. 33.
    Rollins BJ, Yoshimura T, Leonard EJ, Pober JS. Cytokine-activated human endothelial cells synthetize and secrete a monocyte chemoattractant, MCP-1/JE. Am. J. Pathol. 1990; 136(6): 1229–1233.PubMedGoogle Scholar
  34. 34.
    Konkle BA, Shapiro SS, Asch AS, Nachman RL. Cytokine-enhanced expression of glycoprotein Ibalpha in human endothelium. J. Biol. Chem. 1990; 265(32): 19833–19838.PubMedGoogle Scholar
  35. 35.
    Bevilacqua MP, Stengelin S, Gimbrone-Jr MA, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 1989; 243: 1160–1165.PubMedCrossRefGoogle Scholar
  36. 36.
    Sironi M, Breviario F, Proserpio P, Biondi A, Vecchi A, VanDamme J, Dejana E, Mantovani A. IL-1 stimulates IL-6 production in endothelial cells. J. Immunol. 1989; 142(2): 549–553.PubMedGoogle Scholar
  37. 37.
    Rossi V, Breviario F, Ghezzi P, Dejana E, Mantovani A. Prostacyclin synthesis induced in vascular cells by interleukin-1. Science 1985; 229: 174–176.CrossRefGoogle Scholar
  38. 38.
    Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW, Vercellotti GM. Ferritin: a cytoprotective antioxydant stratagem of Endothelium. J. Biol. Chem. 1992; 267(25): 18148–18153.PubMedGoogle Scholar
  39. 39.
    Otsuka A, Hanafusa T, Kono N, Tarui S. LPS augments HLA-A,B,C molecule expression but inhibits interferon-gamma-induced HLA-DR molecule expression on cultured human endothelial cells. Immunology 1991; 73: 428–432.PubMedGoogle Scholar
  40. 40.
    Maher SE, Karmann K, Min W, Hughes CC, Pober JS, Bothwell AL. Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells. J. Immunol. 1996; 157(9): 3838–3844.PubMedGoogle Scholar
  41. 41.
    Forsyth KD, Chua KY, Talbot V, Thomas WR. Expression of the leukocyte common antigen CD45 by endothelium. J. Immunol. 1993; 150(8): 3471–3477.PubMedGoogle Scholar
  42. 42.
    Seelentag WK, Mermod JJ, Montesano R, Vassali P. Additive effects of IL-1 and TNF alpha on the accumulation of the three granulocyte and macrophage colony-stimulating factor mRNAs in human endothelial cells. EMBO J. 1987; 6(8): 2261–2265.PubMedGoogle Scholar
  43. 43.
    Boutherin-Falson O, Reuse S, Dumont JE, Boeynaems JM. Increased levels of c-fos and c-myc mRNA in ATP-stimulated endothelial cells. Biochem. Biophys. Res. Commun. 1990; 172(1): 306–312.PubMedCrossRefGoogle Scholar
  44. 44.
    Vanhove B, Hofer-Warbinek R, Kapetanopoulos A, Hofer E, Bach FH, deMartin R. Gem, a GTP-binding protein from mitogen-stimulated T cells, is induced in endothelial cells upon activation by inflammatory cytokines. Endothelium 1997; 5: 51–61.PubMedCrossRefGoogle Scholar
  45. 45.
    Dixit VM, Green S, Sarma V, Holzman LB, Wolf FW, O’Rourke K, Ward PA, Prochownik EV, Marks RM. TNA alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J. Biol. Chem. 1990; 265(5): 2973–2978.PubMedGoogle Scholar
  46. 46.
    Anrather J, Csizmadia V, Brostjan C, Soares MP, Bach FH, Winkler H. Inhibition of bovine endothelial cell activation in vitro by regulated expression of a transdominant inhibitor of NF-κB. J. Clin. Invest. 1997; 99(4): 763–772.PubMedGoogle Scholar
  47. 47.
    Hiscott J, Marois J, Garoufalis J, D’Addario M, Roulston A, Kwan I, Pepin N, Lacoste J, Nguyen H, Bensi G, Fenton M. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol. Cell. Biol. 1993; 13: 6231–6240.PubMedGoogle Scholar
  48. 48.
    Cheng Q, Cant CA, Moll T, Hofer-Warbinek R, Wagner E, Birnstiel-ML ML, Bach-FH FH, de-Martin R. NK-kappa B subunit-specific regulation of the I kappa B alpha promoter. J. Biol. Chem. 1994; 269(18): 13551–13557.PubMedGoogle Scholar
  49. 49.
    Pan JL, McEver RP. Regulation of the human P-selectin promoter by Bc1-3 and specific homodimer members of the NF-κB/Rel family. J. Biol. Chem. 1995; 270: 23077–23083.PubMedCrossRefGoogle Scholar
  50. 50.
    Wrighton CJ, Hofer-Warbinek R, Moll T, Eytner R, Bach FH, deMartin R. Inhibition of endothelial cell activation by adenovirus-mediated expression of IκBalpha, an inhibitor of NF-κB. J. Exp. Med. 1996; 183: 1013–1022.PubMedCrossRefGoogle Scholar
  51. 51.
    Bach FH, Ferran C, Hechenleitner P, Mark W, Koyamada N, Miyatake T, Winkler H, Badrichani A, Candidas D, Hancock WW. Accommodation of vascularize xenografts: expression of ‘protective genes’ by donor endothelial cells in a host Th2 cytokine environment. Nature Med. 1997; 3(2): 196–204.PubMedCrossRefGoogle Scholar
  52. 52.
    Dorling A, Stocker C, Tsao T, Haskard DO, Lechler RI. In vitro accommodation of immortalized porcine endothelial cells. Transplantation 1996; 62: 1127–1136.PubMedCrossRefGoogle Scholar
  53. 53.
    Abraham NG, Lavrosky Y, Schwartzman ML, Stoltz RA, Levere RD, Gerritsen ME, Shibahara S, Kappas A. Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. Proc. Natl. Acad. Sci. USA 1995; 92: 6798–6802.PubMedCrossRefGoogle Scholar
  54. 54.
    Brown K, Gestberger S, Carlson L, Franzoso G, Siebenlist U. Control of IκB-a proteolysis by site-specific, signal-induced phosphorylation. Science 1995; 267: 1485–1488.PubMedCrossRefGoogle Scholar
  55. 55.
    Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NK-κB. Nature 1995; 376: 167–170.PubMedCrossRefGoogle Scholar
  56. 56.
    Paul M, Zintz M, Böcker W, Dyer M. Characterization and functional analysis of the rat endothelin promoter. Hypertension 1995; 25(4): 683–687.PubMedGoogle Scholar
  57. 57.
    Cowan PJ, Shinkel TA, Witort EJ, Barlow H, Pearse MJ, D’Apice AJF. Targeting gene expression to endothelial cells in transgenic mice using the human intercellular adhesion molecule 2 promoter. Transplantation 1996; 62(2): 155–160.PubMedCrossRefGoogle Scholar
  58. 58.
    Aird WC, Jahroudi N, Weiler-Guettler H, Rayburn HB, Rosenberg RD. Human von Willebrand factor gene sequences target expression to a subpopulation of endothelial cells in transgenic mice. Proc. Natl. Acad. Sci. USA 1995; 92: 4567–4571.PubMedCrossRefGoogle Scholar
  59. 59.
    Dumont DJ, Yamaguchu TP, Conlon RA, Rossant J, Breitman ML. Tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors. Oncogene 1992; 7(8): 1471–1480.PubMedGoogle Scholar
  60. 60.
    Korhonen J, Lahtinen I, Halmekyto M, Alhonen L, Janne J, Dumont D, Alitalo K. Endothelial-specific gene expression directed by the tie gene promoter in vivo. Blood 1995; 86: 1828–1835.PubMedGoogle Scholar
  61. 61.
    Morishita K, Johnson DE, Williams LT. A novel promoter for vascular endothelial growth factor receptor (flt-1) that confers endothelial-specific gene expression. J. Biol. Chem. 1995; 270(46): 27948–27953.PubMedCrossRefGoogle Scholar
  62. 62.
    Patterson C, Perrella MA, Hsieh CM, Yoshizumi M, Lee ME, Haber E. Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor. J. Biol. Chem. 1995; 270(39): 23111–23118.PubMedCrossRefGoogle Scholar
  63. 63.
    Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science 1995; 268: 1766–1769.PubMedCrossRefGoogle Scholar
  64. 64.
    Schultze N, Burki Y, Lang Y, Certa U, Bluethmann H. Efficient control of gene expression by single step integration of the tetracycline system in transgenic mice. Nature Biotech. 1996; 14: 499–503.CrossRefGoogle Scholar
  65. 65.
    VanAntwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-alpha-induced apoptosis by NF-κB. Science 1996; 274: 787–789.PubMedCrossRefGoogle Scholar
  66. 66.
    Wang CY, Mayo MW, Baldwin AS. TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science 1996; 274: 784–787.PubMedCrossRefGoogle Scholar
  67. 67.
    Beg AA, Baltimore D. An essential role for NF-κB in preventing TNF-alpha-induced cell death. Science 1996; 274: 782–784.PubMedCrossRefGoogle Scholar
  68. 68.
    Grimm S, Bauer MKA, Baeuerle PA, Schulze-Osthoff K. Bc1-2 down-regulates the activity of transcription factor NF-κB induced upon apoptosis. J. Cell. Biol. 1996; 134(1): 13–23.PubMedCrossRefGoogle Scholar
  69. 69.
    Ferran C, Cooper JT, Brostjan C, Stroka DM, Millan MT, Goodman DJ, Bach FH. Expression of a truncated form of the human p55 TNF-receptor in bovine aortic endothelial cells renders them resistant to human TNF. Transplantation Proc. 1996; 28(2): 618–619.Google Scholar
  70. 70.
    Waterworth PD, Cozzi E, Tolan MJ, Langford G, Braidley P, Chavez G, Dunning J, Wallwork J, White D. Pig-to-primate cardiac xenotransplantation. Transplant. Proc. 1997; 29: 899–900.PubMedCrossRefGoogle Scholar
  71. 71.
    Josien R, Pannetier C, Douillard P, Cantarovich D, Menoret S, Bugeon L, Kourilsky P, Soulillou JP, Cuturi-MC MC. Graft-infiltrating T helper cells, CD45RC phenotype, and Th1/Th2-related cytokines in donor-specific transfusion-induced tolerance in adult rats. Transplantation 1995; 60(10): 1131–1139.PubMedCrossRefGoogle Scholar
  72. 72.
    Candinas D, Belliveau S, Koyamada N, Miyatake T, Hechenleitner P, Mark W, Bach FH, Hancock WW. T cell independence of macrophage and natural killer cell infiltration, cytokin production, and endothelial activation during delayed xenograft rejection. Transplantation 1996; 62(12): 1920–1927.PubMedCrossRefGoogle Scholar
  73. 73.
    Charreau B, Tesson L, Soulillou JP, Pourcel C, Anegon I. Transgenesis in rats: technical aspects and models. Transgenic Res. 1996; 5(4): 223–234.PubMedCrossRefGoogle Scholar
  74. 74.
    Yamada K, Sachs DH, DerSimonian H. Human anti-porcine xenogeneic T cell response. Evidence for allelic specificity of mixed leukocyte reaction and for both direct and indirect pathways of recognition. J. Immunol. 1995; 155(11): 5249–5256.PubMedGoogle Scholar
  75. 75.
    Kirk AD, Li RA, Kinch MS, Abernethy KA, Doyle C, Bollinger RR. The human antiporcine cellular repertoire. In vitro studies of acquired and innate cellular responsiveness. Transplantation 1993; 55(4): 924–931.PubMedCrossRefGoogle Scholar
  76. 76.
    Dorling A, Binns R, Lechler RI. Cellular xenoresponses: observation of significant primary indirect human T cell anti-pig xenoresponses using co-stimulator-deficient or SLA class II-negative porcine stimulators. Xenotransplantation 1996; 3: 112–119.CrossRefGoogle Scholar
  77. 77.
    Dorling A, Lombardi G, Binns R, Lechler-RI RI. Detection of primary direct and indirect human anti-porcine T cell responses using a porcine dendritic cell population. Eur. J. Immunol. 1996; 26(6): 1378–1387.PubMedCrossRefGoogle Scholar
  78. 78.
    Murphy PM. Molecular mimicry and the generation of host defense protein diversity. Cell 1993; 72(6): 823–826.PubMedCrossRefGoogle Scholar
  79. 79.
    Campos L, Naji A, Deli BC, Kern JH, Kim JI, Barker CF, Markmann JF. Survival of MHC-deficient mouse heterotopic cardiac allografts. Transplantation 1995; 59(2): 187–191.PubMedCrossRefGoogle Scholar
  80. 80.
    Pescovitz MD, Sachs DH, Lunney JK, Hsu SM. Localization of class II MHC antigens on porcine renal vascular endothelium. Transplantation 1984; 37: 627–630.PubMedCrossRefGoogle Scholar
  81. 81.
    Soulillou JP. Relevant targets for therapy with monoclonal antibodies in allograft transplantation. Kidney Int. 1994; 46(2): 540–553.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Bernard Vanhove
  • Jean-Paul Soulillou

There are no affiliations available

Personalised recommendations