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Dtsch Med Wochenschr 2002; 127(31/32): 1651-1655
DOI: 10.1055/s-2002-33202
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© Georg Thieme Verlag Stuttgart · New York

Gibt es klinisch eine spenderspezifische Toleranz und ist sie messbar?

Is there donor-specific tolerance and can it be measured?F. Geissler1 , H. Witzigmann1 , J. Hauss1 , H. Sollinger2
  • 1Klinik für Abdominal-, Transplantations- und Gefäßchirurgie, (Direktor: Prof. Dr. J. Hauss), Universität Leipzig
  • 2Division of Transplantation, Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA
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Publication History

eingereicht: 11.1.2002

akzeptiert: 26.6.2002

Publication Date:
06 August 2002 (online)

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Glossar

DTH = delayed-type hypersensitivity (Überempfindlichkeit vom Spättyp)

PBMC = peripheral blood mononuclear cells (periphere mononukleäre Zellen)

Obwohl bei Organversagen im Endstadium die Transplantation von parenchymatösen Organen allgemein akzeptiert und erfolgreich praktiziert wird, erweisen sich die erhöhte Inzidenz von lebensbedrohlichen Infektionen [18] [24] und Krebserkrankungen [29], die beide auf die lebenslange Einnahme von Immunsuppressiva zurückzuführen sind, als wesentliche Nachteile. Weiterhin stellt die chronische Abstoßung, die bei vielen Organen zu einem Transplantatversagen führt, ein erhebliches Problem dar [16] [37]. Deshalb ist die medikamentöse Induktion einer spenderspezifischen Toleranz mit Erhaltung einer ansonsten normalen Immunantwort das Ziel in der transplantationsimmunologischen Forschung. Eine wichtige Frage dabei ist, ob es eine solche Toleranz per se bei bestimmten Transplantationspatienten gibt. Zur Beantwortung dieser Frage ist es notwendig, messbare prognostische Kriterien für die Toleranz zu definieren.

Literatur

  • 1 Anderson C C, Matzinger P. Immunity or tolerance: opposite outcomes of microchimerism from skin grafts.  Nat Med. 2001;  7 80-87
    Search in Google Scholar
  • 2 Anderson D, Billingham R E, Lampkin G H, Medawar P. The use of skin grafting to distinquish between monozygotic and dizygotic twins in cattle.  Heredity. 1951;  5 379-397
    Search in Google Scholar
  • 3 Bean M A, Akiyama M, Kodera Y, Dupont B, Hansen J A. Human blood T lymphocytes that suppress the mixed leukocyte culture reactivity of lymphocytes from HLA-B14 bearing individuals.  J Immunol. 1979;  123 1610-1614
    Search in Google Scholar
  • 4 Billingham R E, Brent L, Medawar P B. Actively acquired tolerance of foreign cells.  Nature. 1953;  172 603-608
    Search in Google Scholar
  • 5 Burlingham W. Soluble MHC immunregulation and tolerance: a progress report.  Hum Immunol. 2000;  61 1316-1319
    Search in Google Scholar
  • 6 Burlingham W J, Grailer A P, Fechner J H. et al . Microchimerism linked to cytotoxic T lymphocyte functional unresponsiveness (clonal anergy) in a tolerant renal transplant recipient.  Transplantation. 1995;  59 1147-1155
    Search in Google Scholar
  • 7 Burlingham W J, Kusaka S, Chin L T. et al . Focal infiltrates in kidney allografts: developing a model for clinical transplant tolerance.  Graft. 1999;  2 253-260
    Search in Google Scholar
  • 8 Carrodeguas L, Orosz C G, Waldman W J, Sedmak D D, Adams P W, VanBuskirk A M. Trans vivo analysis of human delayed-type hypersensitivity reactivity.  Hum Immunol. 1999;  60 640-651
    Search in Google Scholar
  • 9 de Bueger M, Bakker A, Van Rood J J, Van der Woude F, Goulmy E. Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocyte-defined non-MHC antigens.  J Immunol. 1992;  149 1788-1794
    Search in Google Scholar
  • 10 Devlin J, Doherty D, Thomson L, Wong T, Donaldson P, Portmann B, Williams R. Defining the outcome of immunosuppression withdrawal after liver transplantation.  Hepatology. 1998;  27 926-933
    Search in Google Scholar
  • 11 Dey B, Sykes M, Spitzer T R. Outcomes of recipients of both bone marrow and solid organ transplants. A review.  Medicine (Baltimore). 1998;  77 355-369
    Search in Google Scholar
  • 12 Geissler F, Jankowska-Gan E, DeVito-Haynes L. et al . Human liver allograft acceptance and the „tolerance assay”: In vitro anti-donor T-cell reactivity shows hyporeactivity to donor cells but, unlike DTH, fails to detect donor linked suppression.  Transplantation. 2001;  27 571-580
    Search in Google Scholar
  • 13 Geissler F, Jankowska-Gan E, Sollinger H. et al . Immunoregulation in a tolerant liver transplant recipient: donor class I HLA triggers linked suppression of DTH.  Transplantation. 2000;  69 172 (Suppl)
    Search in Google Scholar
  • 14 Gianello P, Fishbein J M, Sachs D H. Tolerance to primarily vascularized allografts in miniature swine.  Immunol Rev. 1993;  133 19-44
    Search in Google Scholar
  • 15 Hasek M. Manifestation of vegatative assimilation in adaptation of higher animals to foreign antigens.  Czech Biol. 1954;  3 327-339
    Search in Google Scholar
  • 16 Hayry P. Chronic allograft rejection: an update (Review).  Clin Transplant. 1994;  8 160-161
    Search in Google Scholar
  • 17 Homann D, Holz A, Bot A. et al . Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway.  Immunity. 1999;  11 463-472
    Search in Google Scholar
  • 18 Jamil B, Nicholls K, Becker G J, Walker R G. Impact of acute rejection therapy on infections and malignancies in renal transplant recipients.  Transplantation. 1999;  68 1597-1603
    Search in Google Scholar
  • 19 Josien R, Heslan M, Brouard S, Soulillou J P, Cuturi M C. Critical requirement for graft passenger leukocytes in allograft tolerance induced by donor blood transfusion.  Blood. 1998;  92 4539-4544
    Search in Google Scholar
  • 20 Kabelitz D. Apoptosis, graft rejection, and transplantation tolerance.  Transplantation. 1998;  65 869-875
    Search in Google Scholar
  • 21 Keunecke C, Rothenpieler U, Zanker B, Schneeberger H, Illner W D, Theodorakis J, Stangl M, Land W. Mycophenolate mofetil monotherapy: an example of a safe nephrotoxicity/atherogenicity-free immunosuppressive maintenance regimen in a selected group of kidney-transplanted patients.  Transplant Proc. 2000;  32 6S-8S
    Search in Google Scholar
  • 22 Ko S, Deiwick A, Jager M D. et al . The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat.  Nat Med. 1999;  5 1292-1297
    Search in Google Scholar
  • 23 Kusaka S, Grailer A P, Fechner J H. et al . Clonotype analysis of human alloreactive T cells: a novel approach to studying peripheral tolerance in a transplant recipient.  J Immunol. 2000;  164 2240-2247
    Search in Google Scholar
  • 24 Lassner D, Geissler F, Bosse S. et al . Diagnosis and monitoring of acute cytomegalovirus infection in peripheral blood of transplant recipients by nested reverse transcriptase polymerase chain reaction (RT-PCR).  Transpl Int. 2000;  13 366-371
    Search in Google Scholar
  • 25 Mazariegos G V, Reyes J, Marino I R, Demetris A J, Flynn B, Irish W, McMichael J, Fung J J, Starzl T E. Weaning of immunosuppression in liver transplant recipients.  Transplantation. 1997;  63 243-249
    Search in Google Scholar
  • 26 Medawar P. A discussion of Immunological tolerance.  Proc Roy Soc. 1956;  146 1-8
    Search in Google Scholar
  • 27 O’Connell P J, Burlingham W J. Donor-dendritic cell persistence in allograft recipients in the absence of immunosuppression.  J Leukoc Biol. 1999;  66 301-305
    Search in Google Scholar
  • 28 Owen R D. Immunogenetic consequences of vascular anastomoses between bovine twins.  Science. 1945;  102 400-404
    Search in Google Scholar
  • 29 Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients.  Clin Transpl. 1998;  147-158
    Search in Google Scholar
  • 30 Sharabi Y, Abraham V S, Sykes M, Sachs D H. Mixed allogeneic chimeras prepared by a non-myeloablative regimen: requirement for chimerism to maintain tolerance.  Bone Marrow Transplant. 1992;  9 191-197
    Search in Google Scholar
  • 31 Starzl T E. Cell migration and chimerism - a unifying concept in transplantation - with particular reference to HLA matching and tolerance induction.  Transplant Proc. 1993;  25 8-12
    Search in Google Scholar
  • 32 Starzl T E, Demetris A J, Trucco M. et al . Systemic chimerism in human female recipients of male livers.  Lancet. 1992;  340 876-877
    Search in Google Scholar
  • 33 Steinmuller D. Immunization with skin isografts taken from tolerant mice.  Science. 1967;  158 127-129
    Search in Google Scholar
  • 34 Uehling D T, Hussey J L, Weinstein A B, Wank R, Bach F H. Cessation of immunosuppression after renal transplantation.  Surgery. 1976;  79 278-282
    Search in Google Scholar
  • 35 VanBuskirk A M, Burlingham W J, Jankowska-Gan E. et al . Human allograft acceptance is associated with immune regulation.  J Clin Invest. 2000;  106 145-155
    Search in Google Scholar
  • 36 VanBuskirk A M, Wakely M E, Sirak J H, Orosz C G. Patterns of allosensitization in allograft recipients: long-term cardiac allograft acceptance is associated with active alloantibody production in conjunction with active inhibition of alloreactive delayed-type hypersensitivity.  Transplantation. 1998;  65 1115-1123
    Search in Google Scholar
  • 37 Vazquez M A. Chronic rejection of renal transplants: new clinical insights.  Am J Med Sci. 2000;  320 43-58
    Search in Google Scholar
  • 38 Warren E H, Greenberg P D, Riddell S R. Cytotoxic T-lymphocyte-defined human minor histocompatibility antigens with a restricted tissue distribution.  Blood. 1998;  91 2197-2207
    Search in Google Scholar
  • 39 Wood K J, Sachs D H. Chimerism and transplantation tolerance: cause and effect.  Immunol Today. 1998;  17 584-587
    Search in Google Scholar
  • 40 Yasumura T, Kahan B D. Prolongation of rat kidney allografts by pretransplant administration of donor antigen extract or whole blood transfusion combined with a short course of cyclosporine.  Transplantation. 1983;  36 603-609
    Search in Google Scholar
  • 41 Zavazava N, Kabelitz D. Alloreactivity and apoptosis in graft rejection and transplantation tolerance.  J Leukoc Biol. 2000;  68 167-174
    Search in Google Scholar

Dr. Felix Geissler

Universität Leipzig, Klinik für Abdominal-, Transplantations und Gefäßchirurgie

Liebigstraße 20a

04103 Leipzig

Phone: 0341/9717200

Fax: +49/341/9717209

Email: felix@medizin.uni-leipzig.de