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  • 1
    Electronic Resource
    Electronic Resource
    Long-term small bowel allograft function induced by short-term FK 506 application is associated with split tolerance (2000)
    Springer
    Transplant international 13 (2000), S. S532 
    Details
    ISSN: 1432-2277
    Keywords: Key words Small bowel transplantation ; Split tolerance ; FK 506 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Functional long-term allograft survival after experimental small bowel transplantation (SBT) is limited by chronic rejection. Initial application of high-dose FK 506 has been shown to induce stable long-term graft function. In order to examine whether this long-term function is associated with donor-specific tolerance, we analyzed the functional status of recipient T cells in vivo and in vitro. One-step orthotopic SBT was performed in the allogeneic Brown Norway (BN)-to-Lewis rat strain combination. FK 506 was given daily at a dose of 2 mg/kg from days 0–5 in the rejection model and from days 0–9 in the long-term functional model. Mean survival time in the rejection model was 98 ± 2.8 days. Histological examination of these small bowel allografts disclosed signs of chronic rejection. In contrast, all animals of the long-term functional model survived long term ( 〉 250 days) without clinical signs of chronic rejection. The latter model, furthermore, produced evidence of donor-specific tolerance. Whereas heterotopic Dark Agouti (DA) hearts were rejected regularly within 7 days, BN hearts survived indefinitely ( 〉 70 days). In vitro, mixed leukocyte reactivity of CD4 + T cells was similarly strong against donor (BN) antigens as against third-party (DA) antigens. The split tolerance revealed by our in vivo and in vitro results enabled acceptance of both the small bowel allograft without signs of chronic rejection and of donor-specific heart allografts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050396
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  • 2
    Electronic Resource
    Electronic Resource
    Different kinetics of donor cell populations after isolated liver and combined liver/small bowel transplantation (2000)
    Springer
    Transplant international 13 (2000), S. S537 
    Details
    ISSN: 1432-2277
    Keywords: Key words Chimerism ; Graft chimerism ; Tolerogenic effect of liver graftsRID=""ID="" 〈E5〉Correspondence to〈/E5〉 S. Löffler
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spontaneous tolerance induction after liver transplantation also supports additional transplants, e. g. a small bowel graft, from the same donor (tolerogenic effect). Chimerism serves as a possible explanation of this phenomenon. Isolated liver (LTx) and combined liver/small bowel transplantation (LSBTx) are compared. LSBTx and LTx were performed in the BN → LEW rat strain combination without immunosuppression. Parenchymal damage during rejection was monitored by sequential standard histology. Donor/recipient populations were identified and further differentiated for immunhistochemical single and double staining. A small number of donor specific leukocytes can be detected on all days in host organs (microchimerism). A significantly larger donor leukocyte population survives long-term in the sinusoids of liver (graft chimerism). Sinusoidal donor leukocytes survive rejection and recover in number after tolerance induction. Rejection of liver allografts and infiltration by host leukocytes are more pronounced after LSBTx than after LTx. Accordingly, during rejection a steeper decline of sinusoidal donor leukocytes is observed after LSBTx and recovery after tolerance induction is not as marked. Microchimerism apparently plays no significant role in either transplantation model. The number of sinusoidal donor leukocytes, however, mirrors closely host immune responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050397
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  • 3
    Electronic Resource
    Electronic Resource
    “Tolerogenic effect” of the liver for a small bowel allograft (2000)
    Springer
    Transplant international 13 (2000), S. S123 
    Details
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Small bowel transplantation ; Tolerogenicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A newly developed liver/small bowel transplantation model (LSBTx) was used to investigate the tolerogenic effect of a liver allograft toward a simultaneously transplanted small bowel. Small bowel transplantation (SBTx) under high-dose immunosuppression was compared to LSBTx with a lower FK506 dosage. Syngeneic Lewis [(LEW) to LEW] and two fully allogeneic rat strain combinations (Brown Norway-to-LEW and Dark Agouti-to-LEW) were used. Clinical course and histological findings after SBTx demonstrated a chronic rejection of the small bowel allograft within 100 days. However, after LSBTx long-term acceptance (〉 150 days) was achieved after a transient rejection crisis, although initial immunosuppression was significantly lower. Furthermore, indicator heart transplantations demonstrated the induction of donor-specific tolerance in both allogeneic strain combinations. In contrast to other LSBTx rat models, these results reflect observations after human LSBTx, in which the rate of acute and chronic rejection is also significantly lower than after human SBTx.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050296
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  • 4
    Electronic Resource
    Electronic Resource
    Donor-derived alloantigen-presenting cells persist in the liver allograft during tolerance induction (2000)
    Springer
    Transplant international 13 (2000), S. 12-20 
    Details
    ISSN: 1432-2277
    Keywords: Key words Liver/small bowel transplantation ; Tolerance ; Dendritic cells ; Kupffer cells ; Antigen-presenting cells ; Chimerism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The predictive value of chimerism was evaluated in three different transplantation models in the rat without immunosuppression: small bowel- (SBTx), liver- (LTx), and liver/small bowel transplantation (LSBTx) were performed in the Brown Norway (BN)-to-Lewis- (LEW) strain combination. Immunohistochemistry and flow cytometry were used to identify donor cells in the recipient's spleen. Their number did not change significantly during transient rejection or tolerance after LTx and LSBTx. However, the amount of donor-derived nonparenchymal cells within the liver allograft including antigen-presenting cells (APCs), such as dendritic and Kupffer cells, clearly mirrored the recipient's immune status: as expected, their number decreased during rejection, but recovered considerably during and after tolerance induction. We conclude that donor cells in the periphery of the recipient correlate with the presence of the allograft, but do not seem to influence graft acceptance actively. However, the kinetics of the detected donor APC population in the liver suggests their important role in modifying the recipient's immune response towards tolerance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050002
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  • 5
    Electronic Resource
    Electronic Resource
    391. Mikrochirurgische Modelle als Basis präklinischer Transplantationsforschung (1983)
    Springer
    Langenbeck's archives of surgery 361 (1983), S. 924-924 
    Details
    ISSN: 1435-2451
    Keywords: Microsurgery ; Organ transplantation ; Mikrochirurgie ; Organtransplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Aufbauend auf Grundnahttechniken lassen sich mit optischen Hilfsmitteln und mikrochirurgischen Methoden größere Operationen an Ratten durchführen. Mit den mikrochirurgischen Modellen Gefäß-, Herz-, Dünndarm-, Niere-, Pankreas- und Lebertransplantation können mit Inzuchtstämmen grundsätzliche Phänomene wie Transplantatabstoßung (HVGR) bzw. Transplantat gegen Wirt Reaktion (GVHR) analysiert werden. Die Stärke dieser Reaktionen ist abhängig 1. vom Histoinkompatibilitätsgrad, 2. von der Menge des allogenen Gewebes, 3. von der Transplantatlokalistation und 4. von der Manipulation des Immunsystems von Spender und Empfänger. Die voll physiologischen orthotopen Modelle haben dabei die größte präklinische Relevanz.
    Notes: Summary Using simple suture technqiues as a basis, it is possible to carry out major operations in rats using microsurgical methods and magnifying glasses. The microsurgical models of vessels, heart, small intestine, kidney, pancreas and liver transplantation enable us to analyse graft rejection (HVGR) and graft versus host reaction (GVHR), expecially in inbred rat strains. The strength of these reactions is dependent upon 1. the degree of histo-incompatibility, 2. the quantity of allogeneic material, 3. the graft localization and 4. the immunological manipulation of donor and recipient. The physiological orthotopic models are of greatest preclinical relevance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01276217
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