Observations of orthotopic liver transplantation in the pig.

Abstract

BRITISH certain of these changes occurred to a lesser degree in stress involution. The stress-involuted thymuses in our study showed the well-known change of cortical atrophy (Hammar, 1921), cystic Hassall's corpuscles, which have been observed in the involuted thymuses of guinea-pigs given cortisone or x-irradiation (Blau, 1965), and an increased percentage area of epithelial cell aggregates, these also being regarded by Lattes (1962) as associated with stress. The nature of these epithelial aggregates remains uncertain. Their appearances may be due simply to loss of lymphocytes with condensation of reticuloepithelial cells, or they may represent hyperplasia of reticuloepithelial cells, perhaps as a reaction to stress. The fact that these epithelial aggregates are seen to some degree in stressed thymuses makes it unlikely that they have any unique relation to systemic lupus erythematosus.The finding that certain of the thymic changes in systemic lupus erythematosus are an exaggeration, albeit gross, of those present in stress involution is in keeping with the prolonged and often debilitating course of the disease, the long terminal stages, and intense treatment with "thymolytic " drugs such as corticosteroids and mercaptopurines. However, we would emphasize that our series contained three surgically resected thymuses, two of which were from patients who had not received " thymolytic " drugs, yet both showed changes as pronounced as others in the series. On the other hand, the greatly increased numbers of plasma cells in the thymus in systemic lupus erythematosus and the presence of germinal centres in the medulla in two of the cases could not be accounted for by stress involution, and point rather to an immune (probably autoimmune) reaction within the thymus (Goldstein, 1966).C jr interpretation is that the thymus in systemic lupus erythematosus is a target organ. There is histological evidence of extreme stress involution and of an autoimmune reaction which could augment changes usually associated with stress involution. SummayStructural changes in the thymus were assessed by a quantitative method in 13 patients with systemic lupus erythematosus and in two groups of control cases representing minimal stress (94 cases) and stress involution (104 cases).The changes of stress involution included reduction of cortex, epithelial cell aggregates in the medulla, and cystic Hassall's corpuscles. In systemic lupus erythematosus there was pronounced lymphocytic depletion resulting in complete cortical atrophy and disorganization of the medulla. A large proportion of the medulla (mean 36%) was occupied by epithelial cell aggregates, and there was a high proportion (89%) of cystic Hassall's corpuscles; moreover, there were greatly increased numbers of plasma cells, and germinal centres were present in two cases.Our interpretation is that the thymus in systemic lupus erythematosus is a target organ. There is histological evidence of extreme stress involution and of an autoimmune reaction which could augment changes usually...

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

“…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.…”

The [ldquo ]privileged[rdquo ] liver and hepatic tolerogenicity

“…It also is important to note that cessation of therapy was not followed by a graft versus host reaction." 12 The liver allograft was subsequently shown to selfinduce permanent tolerance without immunosuppression in at least 3 species: unpredictably in a significant minority of randomly paired outbred pigs, [13][14][15] invari-ably with a small number of strain combinations of inbred rats, 16,17 and in at least 50% of experiments in about 85% of all tested mouse strain pairings. 18 The self-induced tolerance is antigen-specific: ie, extends to other donor tissues and organs.…”

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

“…The immunological advantage of the liver relative to other organs includes a greater ease of inducing the acceptance of hepatic allografts or xenografts after a limited course of immunosuppression (4,25,132) or in swine (133)(134)(135) and some rat strain combinations (136,137) with no treatment at all. In addition, the transplanted liver graft is relatively resistant to the preformed antigraft antibodies that cause hyperacute rejection of the kidney and heart (138)(139)(140)(141).…”