Some Peculiarities of the Survival Time of Skin Homografts

Zotikov, E. A.; Budik, V. M.; Puza, A

doi:10.1111/j.1749-6632.1960.tb23189.x

Cited by 25 publications

(4 citation statements)

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“…This finding was later confirmed, although again, the grafts were relatively small [ 31 – 33 ]. The opposite was observed when skin grafts were increased considerably in size in proportion to the size of the animal so that greater than approximately twenty percent of the total skin area was transplanted [ 32 , 34 – 37 ]. These early studies of skin graft rejection indicated that very small grafts were more slowly rejected than moderate size grafts but that markedly increasing the size of the skin graft prolonged survival.…”

Section: High Dose Tolerance In Transplantationmentioning

confidence: 99%

“…More recently, in clinical composite tissue transplantation, where skin is transplanted as a component of a much larger tissue mass, skin survival is enhanced [ 82 ] compared to that of skin transplanted alone [ 83 ], supporting older anecdotal evidence that large experimental skin grafts in human burns patients survived considerably longer than small grafts [ 32 , 34 ]. Overall, it is becoming clearer from these smaller studies and large-scale analyses that reductions in rejection rates are not only associated with liver tolerogenicity, but may be related to the antigen load of organs transplanted instead.…”

Section: High Dose Tolerance In Transplantationmentioning

confidence: 99%

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Liver Transplant Tolerance and Its Application to the Clinic: Can We Exploit the High Dose Effect?

Cunningham

Sharland

Bishop

2013

Clinical and Developmental Immunology

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The tolerogenic properties of the liver have long been recognised, especially in regard to transplantation. Spontaneous acceptance of liver grafts occurs in a number of experimental models and also in a proportion of clinical transplant recipients. Liver graft acceptance results from donor antigen-specific tolerance, demonstrated by the extension of tolerance to other grafts of donor origin. A number of factors have been proposed to be involved in liver transplant tolerance induction, including the release of soluble major histocompatibility (MHC) molecules from the liver, its complement of immunosuppressive donor leucocytes, and the ability of hepatocytes to directly interact with and destroy antigen-specific T cells. The large tissue mass of the liver has also been suggested to act as a cytokine sink, with the potential to exhaust the immune response. In this review, we outline the growing body of evidence, from experimental models and clinical transplantation, which supports a role for large tissue mass and high antigen dose in the induction of tolerance. We also discuss a novel gene therapy approach to exploit this dose effect and induce antigen-specific tolerance robust enough to overcome a primed T cell memory response.

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Section: High Dose Tolerance In Transplantationmentioning

confidence: 99%

Section: High Dose Tolerance In Transplantationmentioning

confidence: 99%

Liver Transplant Tolerance and Its Application to the Clinic: Can We Exploit the High Dose Effect?

Cunningham

Sharland

Bishop

2013

Clinical and Developmental Immunology

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“…At least three possibilities exist: (a) a reduced number of reactive donor cells is available at any given site because of dilution by host cells; (b) the reactive cells are paralyzed in the presence of excess antigens from the host; and (c) the reaction involves weak antigens of the host (26,27). With regard to the second possibility, it is known that there is a delay in the rejection of skin grafts when very large homografts are applied, due presumably, to the liberation of large amounts of antigen (28).…”

Section: Spontaneous Skinmentioning

confidence: 99%

Homologous Disease in the Adult Rat: A Model for Autoimmune Disease*

Šťastný

Ziff

1962

Annals of the New York Academy of Sciences

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confidence: 92%

Experiments With Skin Transplantation, Runt Disease, and Parabiosis in a New Inbred Rat Strain

Matter

Wharton

1962

Annals of the New York Academy of Sciences

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Bailey (1960), using the Holtzman albino rat, found that large homografts survived longer than small area grafts and concluded that his findings were comparable with those of Zotikov and Budik (1960). Matter and Chambler (1962), however, employing the same strain of Holtzman rat in their experiments, achieved equal survival times (100 days) in both large and small skin transplants and concluded that a state of histocompatibility must therefore exist. Since there are only a few inbred strains reported, other than in mice, an exact study of the degree of inbreeding in the Holtzman strain was therefore initiated.The Holtzman rat, commonly used in research, has been bred in a closed random system for 16 years. Five years ago the Holtzman Co. in Madison, Wis., opened a subsidiary firm in Houston, Texas. Since then the Houston branch has maintained a completely separate stock and has also used random selection for breeding purposes.A strain of rats with a high degree of genetic similarity can be obtained after 20 consecutive generations of brother-sister mating (Billingham and Silver, 1959). The Holtzman rat has been bred in a closed random system, and many more generations were necessary to reach a state of isogenicity.Therefore, skin transplantation, runt disease, and parabiosis were used as biological indicators in assessing the degree of histocompatibility.As yet, a reliable genetic test is not available to prove uniformity. Experiment 1. Skin TransplantationHoltzman rats weighing approximately 200 gm. were employed as indicated below. Homografts with an area of 40 sq. cm. were applied to the back of the host as described previously (Matter and Chambler, 1962). The red Oklahoma King rat was used for control experiments. Sex difference was observed throughout the experiments to avoid graft exchange between identical littermates.Houston rats. This set of 49 rats was divided into a set of 28 with male hosts and female donors and a set of 21 with female hosts and male donors. Forty-seven transplants survived 60 days. At that time 21 rats were used for further experiments. The remaining 26 carried their graft for more than 100 days (FIGURE 1A).One rat died 12 days after grafting with an intact donor skin and could not be followed. Another female host rejected its male donor skin after 44 days. I t was felt that this single failure was not significant enough, however, to in.. dicate a sex-linked incompatibility as described in other inbred strains of mice and rats (Eichwald and Silmser, 1955). 611

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Some Peculiarities of the Survival Time of Skin Homografts

Cited by 25 publications

References 1 publication

Liver Transplant Tolerance and Its Application to the Clinic: Can We Exploit the High Dose Effect?

Liver Transplant Tolerance and Its Application to the Clinic: Can We Exploit the High Dose Effect?

Homologous Disease in the Adult Rat: A Model for Autoimmune Disease*

Experiments With Skin Transplantation, Runt Disease, and Parabiosis in a New Inbred Rat Strain

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