Gibt es klinisch eine spenderspezifische Toleranz und ist sie messbar?

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
• 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
• 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
• 4 Billingham R E, Brent L, Medawar P B. Actively acquired tolerance of foreign cells.  Nature. 1953;  172 603-608
• 5 Burlingham W. Soluble MHC immunregulation and tolerance: a progress report.  Hum Immunol. 2000;  61 1316-1319
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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)
• 14 Gianello P, Fishbein J M, Sachs D H. Tolerance to primarily vascularized allografts in miniature swine.  Immunol Rev. 1993;  133 19-44
• 15 Hasek M. Manifestation of vegatative assimilation in adaptation of higher animals to foreign antigens.  Czech Biol. 1954;  3 327-339
• 16 Hayry P. Chronic allograft rejection: an update (Review).  Clin Transplant. 1994;  8 160-161
• 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
• 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
• 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
• 20 Kabelitz D. Apoptosis, graft rejection, and transplantation tolerance.  Transplantation. 1998;  65 869-875
• 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
• 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
• 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
• 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
• 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
• 26 Medawar P. A discussion of Immunological tolerance.  Proc Roy Soc. 1956;  146 1-8
• 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
• 28 Owen R D. Immunogenetic consequences of vascular anastomoses between bovine twins.  Science. 1945;  102 400-404
• 29 Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients.  Clin Transpl. 1998;  147-158
• 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
• 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
• 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
• 33 Steinmuller D. Immunization with skin isografts taken from tolerant mice.  Science. 1967;  158 127-129
• 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
• 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
• 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
• 37 Vazquez M A. Chronic rejection of renal transplants: new clinical insights.  Am J Med Sci. 2000;  320 43-58
• 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
• 39 Wood K J, Sachs D H. Chimerism and transplantation tolerance: cause and effect.  Immunol Today. 1998;  17 584-587
• 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
• 41 Zavazava N, Kabelitz D. Alloreactivity and apoptosis in graft rejection and transplantation tolerance.  J Leukoc Biol. 2000;  68 167-174