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LPR mice with immunosuppressive compound FK506
WS22-3 "3 MECHANISMS OF LONG-TERM CARDIAC ALLOGRAFT ACCEPTANCE BY SHORT-TERM TREATMENT WITH FK506 IN THE RAT. K.NAKAJIMA, T.OCHIAI, K.SAKAMOTO, T.ASANO, K.ISONO Department of Surgery, School of Medicine, Chiba University, Chiba, Japan Short-term treatment with FK506 resulted in indefinite cardiac allograft survival in the rat. The present study was undertaken to reveal the mechanisms of induction and maintenance of long-term allograft acceptance by FK506. The primary eifect of FK506 was exerted on responder lymphocyZes reacting to the donor antigens in the induction phase. Cell and serum transfer experiments suggested that donor strain-specific suppressor cells and humoral factors were induced by treatment with FK506 in the presence of allografts, and that they played at least partial roles in the maintenance of long-term allograft acceptance.
WS22-4 I M M U N O S U P P R E S S I V E EFFECT OF FK506(FK) ON THE RAT LIVER A L L O G R A F T S S. 7suchimoto, K. Kusumoto, Y. Nakajima, A. Kakita, J. Uchino, T. Natori, M. Aizawa Department of Surgery and Pathology, H o k k a i d o University, 5apporo, Japan Immunosuppressive effect of FK on the rat liver a l l o g r a f t s ( A C i to LEW) and its m e c h a n i s m of tolerance were investigated. Liver was grafted o r t h o t o p i c a l l y by the modified method of Kamada. FK was injected i.m. from the day of grafting for 2 weeks. All the grafts on the untreated recipients were acutely rejected within 2 weeks but 80% and 60% could survive more than I00 days by the injection of 1.0 and 0.32 mg/kg/day of FK, respectively. ACI skin graft(SG) could survive on the lon 8 survivors (LS). Adoptive transfer of spleen cells from LS could also induce the prolonged survival of the ACI SG like the third party SG in the irradiated LEW. In the MLR assay(LS anti ACI), s i g n i f i c a n t suppression was observed, but by adding the lymph node cells from L$ into MLR(untreated LEW anti ACI), suppression was not encountered. Accordingly, FK induced donor specific tolerance, but its m e c h a n i s m is supposed to be different from that of CyA and belong to the deletion type rather than the active suppression.
W S 2 2 - 5 *4 E X P E R I M E N T A L T R E A T M E N T OF A U T O I M M U N E M R L / L P R MICE WITH I M M U N O S U P P R E S S I V E C O M P O U N D FKS06 K.Yamamoto, A.Mori, T.Nakahama, M.Ito $, H . O k u d a i r a and T.Miyamoto. D e p a r t m e n t o f M e d i c i n e and Physical Therapy. F a c u l t y of Medicine, University of Tokyo, Tokyo, Japan and Central Institute for Experimental Animals . A newly developed immunosuppressive drug, FKSO6(Fujisawa, Japan) is know to inhibit T cell immunity such as IL-2 producution or organ transplantation rejections. We h a v e e v a l u a t e d the action of this compound in MRL/lpr mice which develop severe autoimmune diseases. Eight week old female MRL/lpr mice were started to be injected daily with 2mg/kg(high dose), 0.8mg/kg(medium dose), 0.2mg/kg(low dose), or solvent only(control). Survival times of mice were prolonged in the medium and high dose treatment groups. The lymphonode swelling was dramatically prevented with the high dose treatment. The increasing proteinuria was also suppressed in the high dose group. FACS a n a l y s i s revealed that the treatment reduced the percentage of T cells as well as total cellular numbers in the spleen. Serological studies (anti-DNA antibody etc.), proteinuria, pathological changes of kidney and lung were also evaluted. These results indicate that FKS06 c o u l d b e p o t e n t i a l l y used for the treatment of autoimmune diseases.
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WS22-4 I M M U N O S U P P R E S S I V E EFFECT OF FK506(FK) ON THE RAT LIVER A L L O G R A F T S S. 7suchimoto, K. Kusumoto, Y. Nakajima, A. Kakita, J. Uchino, T. Natori, M. Aizawa Department of Surgery and Pathology, H o k k a i d o University, 5apporo, Japan Immunosuppressive effect of FK on the rat liver a l l o g r a f t s ( A C i to LEW) and its m e c h a n i s m of tolerance were investigated. Liver was grafted o r t h o t o p i c a l l y by the modified method of Kamada. FK was injected i.m. from the day of grafting for 2 weeks. All the grafts on the untreated recipients were acutely rejected within 2 weeks but 80% and 60% could survive more than I00 days by the injection of 1.0 and 0.32 mg/kg/day of FK, respectively. ACI skin graft(SG) could survive on the lon 8 survivors (LS). Adoptive transfer of spleen cells from LS could also induce the prolonged survival of the ACI SG like the third party SG in the irradiated LEW. In the MLR assay(LS anti ACI), s i g n i f i c a n t suppression was observed, but by adding the lymph node cells from L$ into MLR(untreated LEW anti ACI), suppression was not encountered. Accordingly, FK induced donor specific tolerance, but its m e c h a n i s m is supposed to be different from that of CyA and belong to the deletion type rather than the active suppression.
W S 2 2 - 5 *4 E X P E R I M E N T A L T R E A T M E N T OF A U T O I M M U N E M R L / L P R MICE WITH I M M U N O S U P P R E S S I V E C O M P O U N D FKS06 K.Yamamoto, A.Mori, T.Nakahama, M.Ito $, H . O k u d a i r a and T.Miyamoto. D e p a r t m e n t o f M e d i c i n e and Physical Therapy. F a c u l t y of Medicine, University of Tokyo, Tokyo, Japan and Central Institute for Experimental Animals . A newly developed immunosuppressive drug, FKSO6(Fujisawa, Japan) is know to inhibit T cell immunity such as IL-2 producution or organ transplantation rejections. We h a v e e v a l u a t e d the action of this compound in MRL/lpr mice which develop severe autoimmune diseases. Eight week old female MRL/lpr mice were started to be injected daily with 2mg/kg(high dose), 0.8mg/kg(medium dose), 0.2mg/kg(low dose), or solvent only(control). Survival times of mice were prolonged in the medium and high dose treatment groups. The lymphonode swelling was dramatically prevented with the high dose treatment. The increasing proteinuria was also suppressed in the high dose group. FACS a n a l y s i s revealed that the treatment reduced the percentage of T cells as well as total cellular numbers in the spleen. Serological studies (anti-DNA antibody etc.), proteinuria, pathological changes of kidney and lung were also evaluted. These results indicate that FKS06 c o u l d b e p o t e n t i a l l y used for the treatment of autoimmune diseases.
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