Homotransplantation of the Liver

Starzl, Thomas E.; Marchioro, Thomas L.; Porter, K. A.; Brettschneider, Lawrence

doi:10.1097/00007890-196707001-00003

Cited by 515 publications

(574 citation statements)

References 7 publications

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“…The same is true, but unpredictably, after liver 30 and, less commonly, kidney transplantation in outbred canines. Moreover, successful liver transplantation induces tolerance with no treatment at all in a significant percentage of outbred pigs as well as several rat 20,31 and virtually all mouse strain combinations 19 .…”

Section: The Role Of Immunosuppressionmentioning

confidence: 84%

The lost chord: microchimerism and allograft survival

et al. 1996

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Recent evidence suggests that passenger leukocytes migrate after organ transplantation and produce persistent chimerism, which is essential for sustained survival of the allografts. Here, Thomas Starzl and colleagues argure that this hematolymphopoietic chimerism provides an important framework for the interpretation of basic and therapeutically oriented transplantataion research.Medawar's characterization of rejection 1 as a host-versus-graft (HVG) reaction (Fig. 1a) was the cornerstone of transplantation immunology. A decade later, this concept was transposed in the context of a graft-versus-host (GVH) reaction (Fig. 1b), in which histoincompatible hematolymphopoietic grafts rejected the immunologically defenseless recipients 2,3 . The resulting assumption that allograft acceptance or rejection could be understood by studying HVG or GVH immunologic responses in isolation led to prompt acceptance of the one-way in vitro tests of immune reactivity as 'minitransplant' surrogates. However, this assumption did not provide a blanket explanation for observations made in animal and human allograft recipients. The one-way paradigmUntil 1959, preparatory donor leukocyte infusion into cytoablated organ recipients was an expected natural extension of the neonatal tolerance model of Billingham, Brent and Medawar 4 and its adult cytoablation analogues 3 . However, when long-term survival of human kidney allografts was accomplished in a few sublethally irradiated recipients without donor leukocyte infusion, and then regularly without cytoreduction under continuous pharmacologic immunosuppression, the need either for chimerism or host preconditioning lost favor.The identification of 'passenger leukocytes' as the primary antigenic component of organs 6,7 led to the belief that their destruction by the host immune system was essential for organ engraftment. When these cells were found to be migratory 8 , including dendritic cells (DCs) 9 , their sensitization effects and presumed elimination at peripheral and intragraft sites was taken for granted. Bone marrow transplantationMajor histocompatibility complex (MHC)-restricted models of acquired tolerance were widely considered to have validated Burnet's prediction that developing lymphocytes could be purged of self-reactive cells before they achieved functional maturity, even following bone marrow transplantation. The alternative possibility that donor and recipient immunecell populations coexisted in neonatally tolerant animals in a mutually nonreactive state while retaining the ability to function collaboratively (e.g. in a joint immune response to infection) was abandoned when no direct experimental support could be found 10 it has since been learned that the outcome in the neonatal tolerance model is highly variable and that a state approaching permanent clonal deletion is uncommon 11 . Recently, it has been shown that the ability of donor-derived leukocyte subsets to proliferate in response to a skin graft challenge was a more critical determinant of neonatal tole...

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Section: The Role Of Immunosuppressionmentioning

confidence: 84%

The lost chord: microchimerism and allograft survival

et al. 1996

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“…The avoidance of pharmacologic manipulation of hemostatis and omission of an external decompressing bypass in the venous sys-34 Arch Surg/Vol 98, Jan 1969 tern undoubtedly helped prevent postoperative thromboembolism such as that seen in earlier cases. 1 If treatment should become necessary for a hemorrhagic diathesis, it should be guided by frequent measures of clotting parameters.…”

Section: Daysmentioning

confidence: 99%

Coagulation During and After Orthotopic Transplantation of the Human Liver

Groth¹,

Pechet²,

Starzl³

1969

Arch Surg

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“…65 Three of our patients had peripheral venous thrombosis, apparently at this phase of convalescence, 56,59,62 with the subsequent development of multiple pulmonary emboli. Evidently a natural rebound hypercoagulability was exaggerated in these cases by the clot-promoting agents administered during operation.…”

Section: Orthotopic Liver Transplantationmentioning

confidence: 72%