Lymphoid/nonlymphoid compartmentalization of donor leukocyte chimerism in rat recipients of heart allografts, with or without adjunct bone marrow.
Lymphoid/nonlymphoid compartmentalization of donor leukocyte chimerism in rat recipients of heart allografts, with or without adjunct bone marrow.
复制标题
具有或不具有辅助骨髓的同种异体心脏移植大鼠受体中供体白细胞嵌合体的淋巴/非淋巴区室化。
DOI：
10.1097/00007890-199808150-00012
复制
发表时间：
1998
期刊：
影响因子：
6.2
通讯作者：
Starzl,TE
中科院分区：
文献类型：
--
作者：
Terakura,M;Murase,N;Demetris,AJ;Ye,Q;Thomson,AW;Starzl,TE
背景。方法：雄性Lewis大鼠→雌性Brown Norway腹腔心脏移植在他克莫司免疫抑制下进行（0-13、20和27天），有或没有供体骨髓，（骨髓亚组）术后1周服用一种可能增强嵌合的药物。我们利用大鼠性别鉴定区y特异性寡核苷酸引物，用聚合酶链反应测定了连续100天静脉血样品和动物死亡后组织样品的供体DNA浓度。结果：在56天内，89%的血液样品检测到嵌合现象，而在100天内没有样品检测到嵌合现象。然而，在95%的天然心脏，80%的皮肤活检标本和23%的脾脏中，在动物被杀死时检测到供体DNA。早期和晚期嵌合的存在和数量与辅助骨髓的使用以及心脏移植血管病变和炎症指数的降低密切相关。嵌合性的进一步增加和/或慢性心脏排斥反应的减少，与单独使用辅助骨髓所取得的效果相比，与使用生长因子Flt-3配体、粒细胞集落刺激因子、结论：先前怀疑的血液和淋巴器官早期嵌合向宿主非淋巴组织主导的转变，与克隆衰竭和免疫冷漠的双重机制是一致的，由抗原迁移和定位控制，这在其他地方被假设为解释器官异体移植接受。
Background.The role of leukocyte migration and chimerism in organ allograft acceptance has been obscured by the lack of information about the late localization of the donor cells.Methods.Male Lewis rat→ female Brown Norway abdominal heart transplantation was performed under tacrolimus immunosuppression (days 0-13, 20, and 27) with or without donor bone marrow and (in bone marrow subgroups) a 1-week postoperative course of a possibly chimerism-enhancing drug. Using rat sex-determining region-Y-specific oligonucleotide primers, we determined the donor DNA concentration by polymerase chain reaction in serial venous blood samples for 100 days and in tissue specimens when animals were killed.Results.Chimerism was detected out to 56 days in 89% of the blood samples but in none of the samples at 100 days. However, donor DNA was detected when animals were killed in 95% of the native hearts, 80% of the skin biopsy specimens, and 23% of the spleens. The presence and quantity of early and late chimerism were strongly correlated the administration of adjunct bone marrow and with a reduction in the vasculopathy and inflammation index in the cardiac allografts. Marginally significant further increases in chimerism and/or reductions in chronic heart rejection beyond those achieved with adjunct bone marrow alone were associated with additional treatment with the growth factors Flt-3 ligand, granulocyte colony-stimulating factor, and a recombinant molecular variant of interleukin-6 (interleukin-6 mutein) but not with hepatocyte growth factor or lisofylline.Conclusions.The previously suspected shift of early chimerism in the blood and lymphoid organs to dominance in host nonlymphoid tissues is consistent with the dual mechanisms of clonal exhaustion and immune indifference, governed by antigen migration and localization, that have been postulated elsewhere to account for organ allograft acceptance.