The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model

Halperin, Edward C.; Knechtle, Stuart J.; Abernethy, Kathy; Saad, Theodore F.; Miller, David; Vernon, Walter B.; Bollinger, R. Randal

doi:10.1016/s0167-8140(87)80152-4

Cited by 15 publications

(8 citation statements)

References 24 publications

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“…The clinical experience obtained through the treatment of Hodgkin's disease [4] has led to the use of TLI in quite different experimental alloand xenogeneic transplantation models [16,211. The improved application of dose and fractionation of TLI [6,18,191 , we found that TLI had some, albeit a variable, effect on graft survival. We have, in an allograft heart transplantation model, found prolongation of graft survival by treatment with MAB OX-19, which is an anti-CD5 antibody (manuscript in preparation), and we therefore wanted to examine the effect of this antibody in the xeno model.…”

Section: Discussionmentioning

confidence: 78%

Treatment with total lymphoid irradiation, cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: Graft survival and morphological analysis

et al. 1990

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Treatment with preoperative total lymphoid irradiation and post-transplant cyclosporin A has been shown to have a synergistic effect on graft survival in allo- and xenotransplantation. Specific monoclonal antibodies against T cells and T cell subpopulations could offer new ways of preventing graft rejection in xenotransplantation. Graft survival and histology were examined after total lymphoid irradiation plus cyclosporin A treatment versus cyclosporin A plus a monoclonal antibody in a concordant, heterotopic, hamster-to-rat heart transplantation model. Preoperative total lymphoid irradiation was given at a dose of 1.25 Gy, 12 times over a period of 3 weeks. Cyclosporin A at a dose of 12.5 mg/kg per day was administered perorally and OX-19, a pan T cell monoclonal antibody, was given as intraperitoneal injections at doses of 100 micrograms or 500 micrograms/kg per day from day 0 until graft rejection. While total lymphoid irradiation alone prolonged graft survival to 9.4 days, total lymphoid irradiation plus cyclosporin A extended graft survival to a mean of 22 days. Cyclosporin alone or combined with the monoclonal antibody could not increase graft survival significantly when compared to untreated animals, which rejected their grafts within 3.7 days. Vascular rejection was the characteristic morphological finding, even after some weeks of excellent graft function. In conclusion, total lymphoid irradiation and cyclosporin A had a synergistic effect on graft survival in this concordant xenotransplantation model, although recent impressive results from other groups could not be reproduced. Total lymphoid irradiation combined with cyclosporin A appears to delay a primary humoral graft rejection, while the mechanism of rejection, judged by histology, stays the same.

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Section: Discussionmentioning

confidence: 78%

Treatment with total lymphoid irradiation, cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: Graft survival and morphological analysis

et al. 1990

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“…The normal predominance of helper/inducer T cells over cytotoxic/suppressor T cells also changes following TLI. Cytotoxic/suppressor T cells predominate in the peripheral circulation [11, 41–46].…”

Section: Clinical Problems To Address In Xenotransplantationmentioning

confidence: 99%

“…TLI also slows B‐cell maturation [47–53]. TLI has been shown to significantly prolong allograft survival of kidney, heart, liver, and skin grafts in mice, rats, dogs, monkeys, baboons, and humans [11, 30–32, 41, 42, 44, 54–58]. It is not surprising, therefore, that researchers have explored the potential use of TLI in xenotransplantation [11].…”

Section: Clinical Problems To Address In Xenotransplantationmentioning

confidence: 99%

Humans as second orangutans: sense or nonsense?

Stoneking

2009

BioEssays

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“…The normal predominance of helper/inducer T cells over cytotoxic/ suppressor T cells also changes following TLI. Cytotoxic/suppressor T cells predominate in the peripheral circulation [11,[41][42][43][44][45][46].…”

Section: Immunologic Effects Of Total Lymphoid Irradiationmentioning

confidence: 99%

“…TLI also slows B-cell maturation [47][48][49][50][51][52][53]. TLI has been shown to significantly prolong allograft survival of kidney, heart, liver, and skin grafts in mice, rats, dogs, monkeys, baboons, and humans [11,[30][31][32]41,42,44,[54][55][56][57][58]. It is not surprising, therefore, that researchers have explored the potential use of TLI in xenotransplantation [11].…”

Section: Immunologic Effects Of Total Lymphoid Irradiationmentioning

confidence: 99%

Non‐human to human organ transplantation:Its biologic basis and a potential role for radiation therapy

Halperin

2001

Intl Journal of Cancer

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SUMMARY There is an inadequate supply of human donor organs for transplantation. Xenotransplantation, the transplantation of organs from non-human animals to humans, is one of the potential solutions to this problem. The pig appears to be the preferred donor. For xenotransplantation to be successful, researchers must deal with three fundamental problems: (1) Hyperacute rejection of porcine organs, related to binding of xenoreactive natural antibodies of the recipient to antigens on the graft's endothelial cells, must be overcome. (2) Transmission of animal pathogens to humans must be prevented. Concern about zoonosis is not only directed to the transplant recipient but also concerns the risk that an infectious agent will be transferred from the recipient to the general population. (3) The xenografted organ must be physiologically compatible with the recipient. The physiological function of a pig organ in a human and its ability to sustain a human are problematic. Total lymphoid irradiation (TLI) and thoraco-abdominal irradiation (TAI) as immunosuppressive modalities have been investigated in rodent-to-rodent, large mammals and non-human primates-to-primates, and pig-to-primate models. In certain clinical situations, TLI and TAI may prove to be important components for the preparation of the xenotransplant recipient. Progress in genetic engineering and cloning may soon lead to clinical trials in xenotransplantation.

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The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model

Cited by 15 publications

References 24 publications

Treatment with total lymphoid irradiation, cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: Graft survival and morphological analysis

Treatment with total lymphoid irradiation, cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: Graft survival and morphological analysis

Humans as second orangutans: sense or nonsense?

Non‐human to human organ transplantation:Its biologic basis and a potential role for radiation therapy

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