ラット腎移植における免疫学的検討 --輸血による移植腎生着延長効果--

Abstract

輸血による移植腎生着延長効果を検討し, その機序を解明することを目的としてin vivoの実験モデルにおいて輸血から移植までの期間, 成分別輸血, strain specificityについて観察した.in vitroでは輸血後のラット血清をリンパ球混合培養に添加した場合の反応抑制効果を検討することにより, 輸血が移植腎の生着延長をもたらす免疫学的機序について考察した.無処置のSDラットに(SD×Wistar) F1ラットの腎を移植した場合の平均生着日数は11.8日であった.Wistarラットの全血1 mlで前処置をおこなったSDラットに, 輸血直後および1～21日目にF1ラット腎を移植したところ, 7～21日目に移植をおこなった場合に有意な生着延長効果が認められ, 最大の効果は9日目におこなった場合であり, その平均生着日数は81.3日以上であった.Wistarラットの全血の成分に類似したimmunogenにてSDラットを前処置したところ, 骨髄リンパ球, 赤血球, 血小板投与群で有意な生着延長効果が認められたが胸腺リンパ球, 血漿投与群では延長効果は認められなかった.SD, Wistar, (SD×Wistar) F1, Fischerラットを用いて, いくつかのrecipientとdonorの組み合わせを作り, donor specificまたはthird partyの全血でrecipientに前処置をおこなったところ, 両者とも移植腎の生着延長効果が認められたが, donor specificな輸血の方がより効果が著明であった.Wistarラットの全血1 mlで前処置を受けたSDラットの血清を, SDラットの脾細胞をresponder cell, (SD×Wistar) Fラットのリンパ節細胞をstimulator cellとするリンパ球混合培養(MLR)に添加したところ反応抑制効果が認められ, その効果は輸血後7日目までに急上昇し, 15日目まで高値を持続した.その後のMLR抑制効果はやや低下傾向を示したが21日目でも50%以上の抑制効果が認められた

An attempt was made to search the mechanism underlying the beneficial effect of blood transfusion effects using the rat renal transplantation model. The mean survival time of (Sprague-Dawley (SD X Wistar)) F1 renal grafts in untreated SD recipients was 11.3 days. Treatment to SD recipients with 1 ml of Wistar whole blood 7 to 21 days prior to transplantation prolonged the mean survival time of (SD X Wistar) F1 renal grafts and maximum effect of prolongation (greater than 81.3 days) was seen when renal transplantation was performed on the 9th day after the treatment. Treatment with Wistar bone marrow cells, red blood cells and platelets 9 days before transplantation prolonged the mean survival time to greater than 41.0 days, greater than 39.3 days and greater than 46.9 days, respectively, whereas no significant effect was observed in the SD recipients pretreated with Wistar thymocytes or with Wistar plasma. Third party blood transfusion also had moderate effects on the prolongation of renal graft survival, but maximum effects of blood transfusion were obtained by donor specific blood transfusion. Sera taken from SD rats at various times after the treatment with Wistar whole blood were assayed for their ability to suppress the mixed leukocyte reaction (MLR) of SD responder and (SD X Wistar) F1 stimulator cells. Suppressor activity rapidly increased with time up to 7 days after blood transfusion. Potent suppression of the MLR was observed with sera obtained between 7 and 15 days after the treatment. Thereafter, suppressor activity gradually decreased but sera obtained even 21 days after the treatment still suppressed the MLR by more than 50%. The experimental results suggest that MLR suppressor factor(s) generated in the recipients by blood transfusion may play an important role in preventing renal graft rejection. Furthermore, not only class II antigens but also class I antigens in the transfusate may be relevant to the immune response which causes a beneficial effect by pretransplant blood transfusion.