Prolonged survival of liver transplants in the pig.

Calne, R. Y.; White, H. J. O.; Yoffa, D. E.; Binns, R. M.; Maginn, R. Reilly; Herbertson, R. M.; Millard, P. R.; Molina, Victor; Davis, D. R.

doi:10.1136/bmj.4.5580.645

Cited by 129 publications

(41 citation statements)

References 4 publications

(4 reference statements)

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“…The subtle changes in the in vivo immunologic repertoire of our bone marrow-primed rat recipients that permmitted challenge hearts to survive did not prevent histopathologically verified chronic rejection of the cardiac grafts. However, the rejection of livers was self-resolving, as has been observed many times before with a variety of organs in small and large animals with and without induction immunosuppression-exemplified by the original pig liver studies (104,109,111,112) and most completely in studies of the exceptionally valuable mouse liver transplantation model (4). These events are compatible with the view that the tolerance induction is an inherently active rather than deletional process (3,5,(58)(59)(60)81,82).…”

Section: Discussionsupporting

confidence: 67%

“…It was already well known by then that canine liver allografts could self-induce tolerance during a 4-month postoperative course of azathioprine (105), and that this occurred even more frequently in untreated outbred pigs (106-110), many of which passed through spontaneously resolving rejection crises (109,111,112). First in pigs (104) and then in rodents (88,113,114), Calne, Zimmermann, and Kamada-and subsequently others (115,116)-showed that the tolerization extended to other donor organs transplanted at the same time or later.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Variable Chimerism, Graft-Versus-Host Disease, and Tolerance After Different Kinds of Cell and Whole Organ Transplantation From Lewis to Brown Norway Rats

MURASE¹,

Starzl²,

TANABE³

et al. 1995

Transplantation

132

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The bidirectional paradigm of tolerance involving reciprocal host vs. graft and graft vs. host reactions was examined after Lewis (LEW) → Brown Norway (BN) transplantation of different whole organs (liver, intestine, heart, and kidney) or of 2.5×10 8 LEW leukocytes obtained from bone marrow, spleen, lymph nodes, and thymus. The experiments were performed without immunosuppression or under 14 daily doses of postoperative tacrolimus, which were continued in weekly doses to 100 days in a "continuous treatment" subgroup, and to 27 days in a short treatment group. Without immunosuppression, all organs and cell suspensions failed to engraft or were acutely rejected. GVHD (usually fatal) was always caused when either the long or short treatment was used for recipients of intestinal grafts and cell suspensions of spleen and lymph nodes. In contrast, both immunosuppressive protocols allowed engraftment of bone marrow cells, liver, heart, and kidney without clinical GVHD, whereas thymus cell suspensions and small doses of whole blood neither engrafted nor caused GVHD. At 100 days, now drug-free for 73 days, the liver, bone marrow, and heart recipients were tolerant in that they accepted all challenge LEW heart and/or liver grafts for 100 more days despite in vitro evidence of donor-specific reactivity (split tolerance). At 200 days, histopathologic studies of the challenge livers were normal no matter what the priming graft. However, the still-beating challenge hearts had a spectrum from normal to severe chronic rejection that defined the tolerogenicity of the original primary grafts: liver best → bone marrow next → heart least. Both the GVHD propensity and tolerogenicity in these experiments were closely associated with recipient tissue chimerism 30 and 100 days after the experiments began. The tissue chimerism was invariably multilineage, but the GVHD outcome was associated with T cell over-representation. These observations provide guidelines that should be considered in devising leukocyte augmentation protocols for human whole organ recipients. The results are discussed in relation to the historical tolerance studies of Billingham, Brent, and Medawar; Good; Monaco; and Calne.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Variable Chimerism, Graft-Versus-Host Disease, and Tolerance After Different Kinds of Cell and Whole Organ Transplantation From Lewis to Brown Norway Rats

MURASE¹,

Starzl²,

TANABE³

et al. 1995

Transplantation

132

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show abstract

“…Garnier in Paris (3) and Terblanche,Peacock and Hobbs in Bristol (4), United Kingdom found that orthotopic liver allografts in pigs sometimes lasted much longer than similar grafts in the dog and we confirmed the findings and studied this remarkable phenomenon that was observed frequently in pigs (5), but consistently between certain strains of rats (6) …”

Section: My Own Interest In Liver Transplantation Had Started When I supporting

confidence: 79%

Early Days of Liver Transplantation

Calne¹

2008

American Journal of Transplantation

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The early days of liver transplantation were exciting, demanding, subject to terrible disappointments and sadness but occasional elation, and a gradual understanding of the factors necessary to achieve a satisfactory operation. In addition, care of an extremely sick patient, the management of the disease, especially if it was infectious or malignant, and the support of the relatives and the transplant team, required a group of loyal, dedicated and above all optimistic members who could see through the repeated unhappy outcomes that eventually most of the problems would be solved. This in fact has come to pass.

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“…The difficulty of engrafting adult thymocytes was first described in mice (21,100), but not with all strain combinations (103), Beyond its relevance to Monaco's research, the two-way paradigm allows reexamination of the literature on the inherent tolerogenicity of whole organs, much of which can be traced back to the 1969 report by Calne et al (104). It was already well known by then that canine liver allografts could self-induce tolerance during a 4-month postoperative course of azathioprine (105), and that this occurred even more frequently in untreated outbred pigs (106)(107)(108)(109)(110), many of which passed through spontaneously resolving rejection crises (109,111,112). First in pigs (104) and then in rodents (88,113,114), Calne, Zimmermann, and Kamada-and subsequently others (115, 116}-showed that the tolerization extended to other donor organs transplanted at the same time or later.…”

Section: Discussionmentioning

confidence: 99%