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Human Natural Killer Cells and Natural Antibodies Recognize Overlapping Molecular Structures on Discordant Xenogeneic Endothelium

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Xenotransplantation

Abstract

Significant progress towards an understanding of the mechanisms of recognition and rejection of xenogeneic grafts has been witnessed in the past few years. Not only has the molecular basis of discordant xenogeneic tissue recognition begun to become unveiled, but transgenic large animals have been generated that express gene products capable of efficiently interfering with some of the phenomena of immune recognition responsible for graft rejection [1, 2]. Pigs expressing human complement-regulating proteins have been successfully generated, and preclinical transplantation models in primate recipients appear promising [2, 3]. It is easy to foresee that the first clinical trials of discordant xenotransplantation will take place in the near future.

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References

  1. Rosengard A.M., Cary N.R., Langford G.A., et al. 1995. Tissue expression of human complement inhibitor, decay accelerating factor, in transgenic pigs. A potential approach for preventing xenograft rejection. Transplantation. 59:1325

    PubMed  CAS  Google Scholar 

  2. McCurry K.R., Kooyman D.L., Alvarado C.G., et al. 1995. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nature Med. 1:423

    Article  PubMed  CAS  Google Scholar 

  3. White D.J, Bradley P., Dunning J., et al. 1995. Hearts from pigs transgenic for human DAF are not hyperacutely rejected when xenografted to primates. Third International Congress for Xenotransplantation. Boston, 1995

    Google Scholar 

  4. Platt J.L., Vercellotti G.M., Dalmasso A.P., et al. 1990. Transplantation of discordant xenografts: a review of progress. Immunol. Today. 11:450

    Article  PubMed  CAS  Google Scholar 

  5. Auchincloss H. Jr. 1988. Xenogeneic transplantation: a review. Transplantation. 46:1

    Article  PubMed  Google Scholar 

  6. Kaufman C.L., Gaines B.A., Ildstad. S.T. 1995. Xenotransplantation. Annu. Rev. Immunol. 13:339

    Article  PubMed  CAS  Google Scholar 

  7. Good A.H., Cooper D.K.C., Malcolm A.J., et al. 1992. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xeno-grafting in humans. Transplant. Proc. 24:559

    PubMed  CAS  Google Scholar 

  8. Oriol R., Ye Y., Koren E., Cooper D.K.C. 1993. Carbohydrate antigens of pig tissues reacting with human natural antibodies as potential targets for vascular hyperacute rejection in pig-to-man organ transplantation. Transplantation 56:1433

    Article  PubMed  CAS  Google Scholar 

  9. Sandrin M.S., Vaughan H.A., Dabkowski P.L., McKenzie I.F.C. 1993. Anti-pig IgM antibodies in human serum react predominantly with Galα(1–3)Gal epitopes. Proc. Natl. Acad. Sci. USA. 90:11391

    Article  PubMed  CAS  Google Scholar 

  10. Galili, U. 1993. Interaction of the natural anti-Gal antibody with α-galactosyl epitopes: a major obstacle for xenotransplantation in humans. Immunol. Today. 14:480

    Article  PubMed  CAS  Google Scholar 

  11. Henion T.R., Macher B.A., Anaraki F., Galili U. 1994. Defining the minimal size of cat-alitically active primate α1,3 galactosyltransferase: structure-function studies on the recombinant truncated enzyme. Glycobiology. 4:193

    Article  PubMed  CAS  Google Scholar 

  12. Sandrin M.S., Fodor W.L., Mouhtouris E., et al. 1995. Enzymatic remodeling of the carbohydrate surface of a xenogeneic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nature Med. 1:1261

    Article  PubMed  CAS  Google Scholar 

  13. Auchincloss H. Jr. 1990. Xenografting: a review. Transplant. Rev. 4:14

    Article  Google Scholar 

  14. Platt J.L., Fischel R.J., Matas A.J., et al. 1991. Immunopathology of hyperacute xenograft rejection in a swine to primate model. Transplantation. 52:214

    Article  PubMed  CAS  Google Scholar 

  15. Thomas F.T., Marchman W., Carobbi A., et al. 1991. Immunobiology of the xenograft response: xenograft rejection in the immunodeficient rodents. Transplant. Proc. 23:208

    PubMed  CAS  Google Scholar 

  16. Arakawa K., Akami T., Okamoto M., et al. 1994. Prolongation of heart xenograft survival in the NK-deficient rat. Transplant. Proc. 26:1266

    PubMed  CAS  Google Scholar 

  17. Inverardi L., Samaja M., Motterlini R., et al. 1992. Early recognition of a discordant xenogeneic organ by human circulating lymphocytes. J. Immunol. 149:1416

    PubMed  CAS  Google Scholar 

  18. Inverardi L., Samaja M., Marelli F., Bender J. R., Pardi R. 1992. Cellular early immune recognition of xenogeneic vascular endothelium. Transplant. Proc. 24:459

    PubMed  CAS  Google Scholar 

  19. Inverardi L., Pardi R. 1994. Early events in cell-mediated recognition of vascularized xenografts: cooperative interactions between selected lymphocyte subsets and natural antibodies. Immunol. Reviews. 141:71

    Article  CAS  Google Scholar 

  20. Blakely M.L., Van Der Werf W.J., Berndt M.C., et al. 1994. Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation. 58:1059

    PubMed  CAS  Google Scholar 

  21. Candinas D., Lesnikoski B.A., Grey S.T., et al. Delayed xenograft rejection (DXR) in complement (c)-depleted T cell-deficient (nude) rat recipients of guinea pig cardiac grafts. Third International Congress for Xenotransplantation. Boston, 1995

    Google Scholar 

  22. Alter B.J., Bach F.H. 1990. Cellular basis of the proliferative response of human T cells to mouse xenoantigens. J. Exp. Med. 171:333

    Article  PubMed  CAS  Google Scholar 

  23. Moses R.D., Pierson R.N. III, Winn H.J., Auchincloss H. Jr. 1990. Xenogeneic proliferation and lymphokine production are dependent on CD4+ helper T cells and self antigen presenting cells in the mouse. J. Exp. Med. 172:567

    Article  PubMed  CAS  Google Scholar 

  24. Dorling A., Binns R., Lechler R.I. 1995. Examination of the direct human T cell xenor-esponse against porcine dendritic cells and identification of inefficient SLA DR recognition. Third International Congress for Xenotransplantation. Boston, 1995

    Google Scholar 

  25. Satake M., Korsgren O., Ridderstad A., et al. 1994. Immunological characteristics of islet cell xenotransplantation in humans and rodents. Immunol. Reviews. 141:191

    Article  CAS  Google Scholar 

  26. Hamelmann W., Gray D.W.R., Cairns T.D.J., et al. 1994. Immediate destruction of xenogeneic islets in a primate model. Transplantation. 58: 1109

    PubMed  CAS  Google Scholar 

  27. Schachner R.D., Ricordi C, Inverardi L. 1995. Xenogeneic discordant islet transplantation: natural antibodies and complement in a human-to-rat model. Transplant. Proc. 27:3318

    PubMed  CAS  Google Scholar 

  28. Inverardi L., Ricordi C. 1996. Transplantation of pancreas and islets of Langerhans: a review of progress. Immunol. Today. 17:7

    Article  PubMed  CAS  Google Scholar 

  29. Murray A.G., Khodadoust M.M., Pober J.S., Bothwell A.L.M. 1994. Porcine aortic endothelial cells activate human T cells: direct presentation of MHC antigens and cost-imulation by ligands for human CD2 and CD28. Immunity. 1:57

    Article  PubMed  CAS  Google Scholar 

  30. Rosenberg A.S., Singer A. 1992. Cellular basis of skin allograft rejection. An in vivo model of immune-mediated tissue destruction. Annu. Rev. Immunol. 10:333

    Article  PubMed  CAS  Google Scholar 

  31. Wanders A., Akyurek M.L., Waltenberger J., et al. 1995. Ischemia-induced transplant atherosclerosis in the rat. Art. Thromb. Vasc. Biol. 15:145

    CAS  Google Scholar 

  32. Wanders A., Akyurek M.L., Waltenberger J., et al. 1993. Impact of ischemia time on chronic vascular rejection in the rat: effects of angiopeptin. Transplant. Proc. 25:2098

    PubMed  CAS  Google Scholar 

  33. Springer T.A. 1994. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 76: 301

    Article  PubMed  CAS  Google Scholar 

  34. Pardi R., Inverardi L., Bender J.R. 1992. Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travelers. Immunol. Today. 13:224

    Article  PubMed  CAS  Google Scholar 

  35. De Lisser H.M., Newman P.J., Albelda S.M. 1994. Molecular and functional aspects of PECAM-1/CD31. Immunol. Today. 15:490

    Article  Google Scholar 

  36. Dustin L.M., Springer T.A. 1989. T cell receptor cross-linking transiently stimulates adhesiveness through LFA-i. Nature. 341:619

    Article  PubMed  CAS  Google Scholar 

  37. Downey G.P., Chan C.K., Lea P., Takai A., Grinstein S. 1992. Phorbol ester-induced actin assembly in neutrophils: role of protein kinase C. J. Cell Biol. 116:695

    Article  PubMed  CAS  Google Scholar 

  38. Hibbs M.L., Jakes S., Stacker S.A., Wallace R.W., Springer T.A. 1991. The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 ß subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site. J. Exp. Med. 174:1227

    Article  PubMed  CAS  Google Scholar 

  39. Pardi R., Inverardi L., Rugarli C, Bender J.R. 1992. Antigen-Receptor complex stimulation triggers protein kinase C-dependent CD11a/CD18-cytoskeleton association in T lymphocytes. J. Cell Biol. 116:1211

    Article  PubMed  CAS  Google Scholar 

  40. Valmu L., Autero M., Siljander P., Patarroyo M., Gahmberg C.G. 1991. Phosphorylation of the ß-subunit of CD11/CD18 integrins by protein kinase C correlates with leukocyte adhesion. Eur. J. Immunol. 21:2857

    Article  PubMed  CAS  Google Scholar 

  41. Diamond M.S., Springer T.A. 1993. A subpopulation of Mac-1 (CD11b/CD18) molecules mediates neutrophil adhesion to ICAM-1 and fibrinogen. J. Cell Biol. 120:545

    Article  PubMed  CAS  Google Scholar 

  42. Dransfield I., Cabanas C, Craig A., Hogg N. 1992. Divalent cation regulation of the function of the leukocyte integrin LFA-1. J. Cell Biol. 116:219

    Article  PubMed  CAS  Google Scholar 

  43. Altieri D.C. 1991. Occupancy of CD11b/CD18 (Mac-i) divalent ion binding site(s) induces leukocyte adhesion. J. Immunol. 147:1891

    PubMed  CAS  Google Scholar 

  44. Landis R.C., Bennett R.I., Hogg N. 1993. A novel LFA-1 activation epitope maps to the I domain. J. Cell Biol. 120:1519

    Article  PubMed  CAS  Google Scholar 

  45. Van Kooyk Y., Weder P., Hogervorst F., et al. 1991. Activation of LFA-1 through Ca2+-dependent epitope stimulates lymphocyte adhesion. J. Cell. Biol. 112:345

    Article  PubMed  Google Scholar 

  46. Gailit J., Ruoslathi E. 1988. Regulation of the fibronectin receptor affinity by divalent cations. J. Biol. Chem. 263:12927

    PubMed  CAS  Google Scholar 

  47. Hermanowski-Vostaka A., van Strijp J.A.G., Swiggard W.J., Wright S.D. 1992. Integrin modulating factor-1: a lipid that alters the function of leukocyte integrins. Cell. 68:341

    Article  Google Scholar 

  48. Chan B.M.C., Hemler M.E. 1993. Multiple functional forms of integrin VLA-2 can be derived from a single α2 cDNA clone: interconversion of forms induced by anti-ß1 antibody. J. Cell. Biol. 120:537

    Article  PubMed  CAS  Google Scholar 

  49. O’Toole E.T., Katagiri Y., Faull R.J., et al. 1994. Integrin cytoplasmic domains mediate inside-out signal transduction. J. Cell. Biol. 124:1047

    Article  PubMed  Google Scholar 

  50. Bertagnolli M.E., Bekerle M.C. 1993. Evidence for the selective association of a subpopulation of GPIIb-IIIa with the actin cytoskeletons of thrombin-activated platelets. J. Cell Biol. 121:1329

    Article  PubMed  CAS  Google Scholar 

  51. Larson R.S., Hibbs M.L., Springer T.A. 1990. The leukocyte integrin LFA-i reconstituted by cDNA transfection in a nonhematopoietic cell line is functionally active and not transiently regulated. Cell Regulation. 1:359

    PubMed  CAS  Google Scholar 

  52. Zweier J.L., Kuppusamy P., Lutty G.A. 1988. Measurement of endothelial cell free radical generation: evidence for a central mechanism of free radical injury in postischemic tissue. Proc. Natl. Acad. Sci. USA. 85:4046

    Article  PubMed  CAS  Google Scholar 

  53. Seccombe J.L, Schaff H.V. 1994. Vasoactive factors produced by the endothelium: physiology and surgical implications. R.G. Landes Company, Austin TX

    Google Scholar 

  54. Lee W.P., Gribling P., De Guzman L., Ehsani N., Watson S.R. 1995. A P-selectin-immu-noglobulin G chimera is protective in a rabbit ear model of ischemia-reperfusion. Surgery. 117:458

    Article  PubMed  CAS  Google Scholar 

  55. Davenpeck K.L., Gauthier T.W., Albertine K.H., Lefer A.M. 1994. Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion. Am. J. Physiol. 267:622

    Google Scholar 

  56. Carden D.L., Young J.A., Granger D.N. 1993. Pulmonary microvascular injury after intestinal ischemia-reperfusion: role of P-selectin. J. Appl. Physiol. 75:2529

    PubMed  CAS  Google Scholar 

  57. Kubes P., Jutila M., Payne D. 1995. Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion. J. Clin. Invest. 95:2510

    Article  PubMed  CAS  Google Scholar 

  58. Sylvestre D.L., Ravetch J.V. 1994. Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade. Science. 265:1095

    Article  PubMed  CAS  Google Scholar 

  59. Inverardi L., Clissi B., Stolzer A., Bender J.R., Pardi R. Overlapping recognition of xenogeneic carbohydrate epitopes by human natural killer cells and preformed natural antibodies, (submitted)

    Google Scholar 

  60. Yokoyama W.M. 1993. Recognition structures on natural killer cells. Curr. Op. Immunol. 5:67

    Article  CAS  Google Scholar 

  61. Trinchieri G. 1989. Biology of natural killer cells. Adv. Immunol. 47:187

    Article  PubMed  CAS  Google Scholar 

  62. Kagi D., Ledermann B., Burki K., et al. 1994. Cytotoxicity mediated by T cells and NK cells is greatly impaired in perforin-deficient mice. Nature. 369:31

    Article  PubMed  CAS  Google Scholar 

  63. Karre K. 1985. Role of target histocompatibility antigens in regulation of NK activity: a reevaluation and a hypothesis. In: Mechanism of Cytotoxicity by NK Cells. Herberman R.B. and Callewaert D.M. (eds), Academic Press; p. 81

    Google Scholar 

  64. Kaufman D.S., Schoon R.A., Leibson P.J. 1993. MHC class I expression on tumor targets inhibits NK cell-mediated cytotoxicity without interfering with target recognition. J. Immunol. 150:1429

    PubMed  CAS  Google Scholar 

  65. Sanchez M.J., Spits H., Lanier L.L., Phillips J.H. 1993. Human natural killer thymocytes and their relation to the T-cell lineage. J. Exp. Med. 178:1857

    Article  PubMed  CAS  Google Scholar 

  66. Sanchez M.J., Muench M.O., Roncarolo M.G. Lanier L.L., Phillips J.H. 1994. Identification of a common T/natural killer cell progenitor in human fetal thymus. J. Exp. Med. 180:569

    Article  PubMed  CAS  Google Scholar 

  67. Wagtmann N., Biassoni R,. Cantoni C, et al. 1995. Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra-and intracellular domains. Immunity. 2:439

    Article  PubMed  CAS  Google Scholar 

  68. Drickamer K. 1993. Calcium-dependent carbohydrate recognition domains in animal proteins. Curr. Op. Struct. Biol. 3:393

    Article  CAS  Google Scholar 

  69. Bezouska K., Yuen C.T., O’Brien J., et al. 1994. Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. Nature. 372:150

    Article  PubMed  CAS  Google Scholar 

  70. Karlhofer F.M., Ribaudo R.K., Yokoyama W.M. 1992. MHC class I alloantigen specificity of Ly 49+ IL2-activated NK cells. Nature. 358:66

    Article  PubMed  CAS  Google Scholar 

  71. Gumperz J.E., Parham P. 1995. The enigma of NK cells. Nature. 378:245

    Article  PubMed  CAS  Google Scholar 

  72. Houchins J.P., Yabe T., McSherry C, Bach F.H. 1994. DNA sequence analysis of NK-G2, a family of related cDNA clones encoding type II integral membrane proteins on human NK cells. J. Exp. Med. 173:1017

    Article  Google Scholar 

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Authors
  1. L. Inverardi
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  2. R. Pardi
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Editors and Affiliations

  1. Immunologist (Surgery), Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, 02129, Boston, Massachusetts, USA

    David K. C. Cooper M.A., M.D., Ph.D., M.S., F.R.C.S. (Associate Member, Scientific Staff) (Associate Member, Scientific Staff)

  2. Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA

    David K. C. Cooper M.A., M.D., Ph.D., M.S., F.R.C.S. (Associate Member, Scientific Staff) (Associate Member, Scientific Staff)

  3. Department of Nephrology, Odense University Hospital, 5000, Odense, Denmark

    Ejvind Kemp M.D. (Professor and Head) (Professor and Head)

  4. Departments of Surgery, Pediatrics and Immunology, Duke University Medical Center, Durham, NC, 27710, USA

    Jeffrey L. Platt M.D. (Joseph W. and Dorothy W. Beard Professor) (Joseph W. and Dorothy W. Beard Professor)

  5. Department of Surgery, University of Cambridge, Cambridge, CB22QQ, UK

    David J. G. White M.A., Ph.D., M.R.C.Path (Immunologist and Lecturer, Director of Research and Development) (Immunologist and Lecturer, Director of Research and Development)

  6. Imutran Laboratories, Cambridge, UK

    David J. G. White M.A., Ph.D., M.R.C.Path (Immunologist and Lecturer, Director of Research and Development) (Immunologist and Lecturer, Director of Research and Development)

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© 1997 Springer-Verlag Berlin Heidelberg

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Inverardi, L., Pardi, R. (1997). Human Natural Killer Cells and Natural Antibodies Recognize Overlapping Molecular Structures on Discordant Xenogeneic Endothelium. In: Cooper, D.K.C., Kemp, E., Platt, J.L., White, D.J.G. (eds) Xenotransplantation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60572-7_10

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  • DOI: https://doi.org/10.1007/978-3-642-60572-7_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64460-3

  • Online ISBN: 978-3-642-60572-7

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