Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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Mixed Chimerism to Achieve Donor-Specific Transplantation Tolerance for Lung Allografts in Rats

혼합형 동종이인자형 키메라쥐에서 특정공여군의 동종 폐이식펀에대한 관용

  • Youm, Wook (Department of Thoracic and Cardiovascular Surgery, Korea Veterans Hospital)
  • 염욱 (한국보훈병원 흉부외과)
  • Published : 1996.07.01
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Abstract

Poor long term patient survival (60% at 2 years) in lung allograft recipients are mainly due to rejection and complications associated with the use of nonspecific immunosuppressants. Better means to achieve waft acceptance is desperately needed. 1 have investigated whether mixed allogeneic chimerism in the form of bone marrow stem cell engraftment would induce donor-specific tolerance for lung allografts. Fisher (F344) and Wistar Forth (WF)rats were lethally irradiated (1100c0y) and reconstituted with a mixture of T-cell depleted syngeneic and allogeneic bone marrow (F344+WFIWF, ACI +F344- F344). After Mixed chimerism was documented by peripheral blood Ipnphocyte typing at 28 days, orthotopic left single lung transplantation was performed, using donor-s ecific or third party allografts. No immunosuppressants were administered. Graft rejection was monitored by chest rentgenography, and con- firmed by histology Mixed chimeric rats accepted lung allografts permanently, and it was not strain specific effect. Tolerance was all or none phenomenon which had nothing to do with the percentage of chimerlsm. Mixed chimeras rejected third party allografts in less than 10 days, a time course similar to that of unmanipulated controls. No acute or chronic rejection was observed in donor specific grafts more than 150 days posttransplant. These data suggest that mixed chimerism in the form of bone marrow stem cell engraftment results in stable, systemic donor-specific transplantation tolerance for lung allografts.

폐이식후의 수용자들의 낮은 생존율은 주로 거부반응 또는 면역억제제 사용에 따른 합병증과 관련이 있다. 따라서 이식편에대한 수용자의 관용을 유도해낼 수 있는 더욱 좋은 방법이 절실히 요구된다. 저자 는 동종의 골수간세포가 주입되어진 혼합동종이 인자형 키메라 쥐에서 특정 동종 공여군의 공여 폐이식 편에대한 관용의 초래여부를 연구하였다. Fisher(F344)와 Wistar Forth(WF)종주의 쥐에서 치사량의 (1100c0y) 방사선조사후 T-임파구를 제거한 동일종주와 동종이인자형 골수의 혼합물로 재구성하였다 (F)44+WFIWF, AC1+F3441F3f4).28일후 말초혈액에서 임파구형의 검사로 혼합형 키메리즘이 확 인된 쥐에서 특정 공여군 또는 제3군의 동종 공여폐로 좌측의 동소 폐이식을시행하였다. 이식후 어떠 한 면역억제제도 투여하지 않았다. 이식편의 거부는 흉부 X선검사로 관찰하였고 조직학적으로 확인하 였다. 혼합형 키메라쥐들은 특정 공여군의 폐들을 받아들였으나 종주들 끼리의 특정효과에의한 것은 아 니었고, 이들에서 150일이상 거부반응을 관찰할 수 없었다. 이식편에대한 관용은 키메리즘의 백분율과 는 관계없이 일어났으며 제3군의 공여폐에대해서 \ulcorner정상대조군에서와 마찬가지로 10일내에 이식편에 대한거부반응이 완료되었다. 이 결과들은흔합형 키메라에서 정상적인 면역기전을 유지하면서도,특정 공여군의 폐이식후 안정적이고_1. 지속적 인, 이식 편에대한 관용이 일어난다는 것을 보여준다.

Keywords

References

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