Induction of specific tolerance by intrathymic injection of recipient muscle cells transfected with donor class I major histocompatibility complex.

Induction of tolerance to allogeneic MHC antigens has been a goal in the field of transplantation because it would reduce or eliminate the need for generalized immunosuppression. Although encouraging results have been obtained in experimental models by exposing recipient thymus to donor cells before transplantation, donor cells are not typically available at that time, and the donor antigens responsible for the effect are poorly defined. In the present study, thymic tolerance was demonstrated without using donor cells. Recipient thymus was injected before transplantation with autologous myoblasts and myotubes that were genetically modified to express allogeneic donor-type MHC class I antigen. Donor-specific unresponsiveness was induced to a completely MHC-disparate liver transplant and to a subsequent donor-type cardiac allograft, but not a third-party allograft. In vitro, recipient CTL demonstrated a 10-fold reduction in killing of donor cells, but not of third-party cells. Our results demonstrate: (1) that recipient muscle cells can be genetically engineered to induce donor-specific unresponsiveness when given intrathymically, and (2) transfected recipient cells expressing only donor MHC class I antigen can induce tolerance to a fully allogeneic donor

Pulmonary Cyst

Pulmonary cysts occupy an important place among diseases of the chest. and their treatment has to be considered by taking into account the pathologic condition of each disease. We have reported here the findings obtained through clinical experience of 6 cases of intrapulmonary bronchial cyst, 36 cases of giant bulla, and 127 cases of spontaneous pneumothorax, who were operated on during the past-odd 10 years at this hospital, with regard to the concept, pathologic condition, developmental mechanism, clinical symptoms, diagnosis and treatment of each disease

Immotile cilia 症候群の徴細型態学的研究

Since presentation of the concepts of the immotile cilia syndrome, much attention has been paid to function and structure of respiratory cilia, many authors have pointed out that ultrastructural abnormality of cilia was attributed to the immotility of cilia. We investigated a woman suspected of the immotile cilia syndrome by electron microscopy, cross sections of cilia obtained from respiratory tract showed lack of dynein arms, radial spokes and central sheath, moreover so-called compound cilia

Examination of Serum Class I Antigen in Allograft Recipient Rats : Origin and control of serum class I antigen

We examined the appearance of DA type (RT1Aa) class I antigen in the serum of rats that had received isogeneic or allogeneic liver grafts (DA into DA, DA into LEW, PVG into DA, PVG into F1 hybrid (DAxPVG). Recipient LEW rats were given either one injection of the anti-CD8 mAb, OX-8, following thymectomy or anti-CD4 mAb (cocktail of OX-35 and OX-38) following thymectomy 3 days prior to liver grafting. We also tested the serum RT1Aa antigen titer of F1 (DAxPVG) recipients after PVG spleen transplantation and the serum RT1Aa antigen titer in the DA rat after hepatectomy and cyclosporin treatment.　　 Replacement of DA liver by PVG lowered transiently the serum level of RT1Aa antigen to 70% of that in normal DA serum, shortly after liver transplantation. However, this titer increased gradually over the level in normal DA serum.　　 A PVG spleen graft to an F1 hybrid recipient resulted in death due to typical GVH disease between 13 and 24 days after spleen transplantation. The RT1Aa antigen titer increased to several times more than that in normal F1 serum throughout the observation period.　　 LEW recipients of DA liver died at 9-11 days (9.8± 1.1 days) due to acute liver rejection. In this combination, the serum level of RT1Aa increased until day 8, reaching a maximum (four times) on day 4. Deletion of either CD8+ or CD4+ T cells by anti-CD8 or anti-CD4 MAb in this transplantation prolonged the survival times of liver grafts for up to 26.8±8.4 and 35.6± 17.9 days, respectively. In the anti-CD8 or anti-CD4 MAb- treated recipients, the serum titer of DA class I antigen was not elevated and there were no differences between the two. Hepatectomy in combination with cyclosporin induced a high titer of liver- derived class I antigen in the serum as long as liver regeneration proceeded.　　 These results suggest that the liver is the principal source of serum class I antigen in rats. Rejection, GVH reaction and liver regeneration increased the serum class I antigen from transplanted liver or host tissue. It is unlikely that this is due to cleavage of membranous class I antigen by class I- reactive CD8+ T cells

Effect of Donor Fasting on Survival of Pancreas and Heart Grafts after Warm Ischemia

Livers from fasted animals are believed to be more vulnerable to ischemic injury than those from fed donors. However, we have recently shown the opposite: livers from fasted rats were more tolerant to ischemic injury. Indeed, the survival rate of 60 min warm ischemic damaged livers increased from 0 to 90% if donor rats were fasted for three days. In this study, we examined how donor fasting affects the outcome of pancreas and heart preservation. BN rats were used as both donors and recipients, and recipients of pancreatic grafts were rendered diabetic prior to transplantation. Pancreatic or heart grafts were subjected to 90 min or 25 min of warm ischemia and were transplanted into the right side of the necks of recipient rats. The viability rate of hearts transplanted from fed donors into fed recipients was only about 11 % (1/9) after transplantation. However, the viability rate with fasted donors was 75% (6/8). The rate of successful pancreatic grafting from fed donors into fed recipients was 28.6% (2/7), and that from fasted donors to fed recipients was 41.7% (5/12). These results confirm that the nutritional status of the donor is an important factor in the outcome of not only liver, but also pancreas and heart preservation during transplantation, although the effect of fasting on pancreatic graft is marginal