Mechanism and modification of rejection of heterografts between divergent species

Abstract

This study was undertaken with several specific objectives: to evaluate the role of preformed heterospecific antibodies in causing hyperacute rejection of whole organs transplanted from dogs to pigs or pigs to dogs; to see how much this abrupt rejection could be mitigated by the antibody depletion that occurs with the use of successive organs; to establish the contribution of coagulation changes to the pathogenesis of this kind of hyperacute rejection; and to determine if there were similarities between abrupt heterograft rejection and hyperacute rejection of homografts in presensitized recipients.

Fig. 1

Rejection times of renal heterografts after transplantation to unmodified recipients (light shading) or after transplantation to animals that had already received a prior kidney, liver or spleen from same donor (black shading). For each experiment, result of control is just to left of that with definitive experiment.

Fig. 2

Pig-to-dog heterotransplantation. Average concentrations of white cells, platelets and antibodies in arterial blood of 31 dogs before and after heterotransplantation of one or more porcine organs.

Fig. 3

Dog-to-pig heterotransplantation. Average concentrations of white cells, platelets, and antibodies in arterial blood of 29 pigs before and after heterotransplantation of one or more canine organs.

Fig. 4

Pig-to-dog heterotransplantation. Arteriovenous gradients of platelets, white cells and clotting parameters across liver and subsequently transplanted kidney from same donor. PTT: partial thromboplastin time; ELT: euglobulin lysis time; solid lines: arterial values; broken lines: results in heterograft venous blood.

Fig. 5

Dog-to-pig heterotransplantation. Arteriovenous gradients of platelets, white cells and clotting parameters across two kidneys sequentially transplanted from same donor. Solid and broken lines indicate arterial and venous blood, respectively. Abbreviations same as Fig. 4.

Fig. 6

Dog-to-pig renal heterotransplantation. Whole blood clotting times in heterotransplantation experiment. At each interval, clotting time in siliconized test tube (upper extent of bar) is compared to that in nonsiliconized test tube (lower extent of bar). For arterial determinations, cross bars are straight: for venous, crossed. Clotting times changed in course of experiment, particularly in venous blood, but alterations tended to be proportionate using siliconized versus nonsiliconized test tubes. Findings were interpreted as evidence against intrarenal contact activation.

Fig. 7

Glomerulus from pig-to-dog renal heterograft at 20 minutes showing engorgement of glomerular capillaries and areas of eosinophilic material (arrows) suggesting thrombus formation. Hematoxylin and eosin. × 400.

Fig. 8

Fibrin deposits in capillaries of glomerulus and peritubular area of biopsy taken from pig-to-dog heterograft at 20 minutes. Stained with fluoresceinated rabbit anti-dog fibrin. × 400.

Fig. 9

Dog IgG deposits in glomerular capillaries from same biopsy shown in Fig. 8. Pattern is same as for fibrin and probably represents entrappment of IgG in thrombus. Stained with fluoresceinated rabbit antidog IgG. × 400.

Fig. 10

Glomerulus from dog-to-pig heterograft at 60 minutes showing polymorpho-nuclear (PMN) leukocyte infiltration (arrows) with no evidence of thrombus formation. Hematoxylin and eosin. × 400.