Synergistic effects of CTLA-4Ig and sirolimus on orthotopic lung-allograft survival and histology
Synergistic effects of CTLA-4Ig and sirolimus on orthotopic lung-allograft survival and histology
复制标题
CTLA-4Ig 和西罗莫司对原位肺同种异体移植物存活和组织学的协同作用
作者：
M. M. Ugurlu;M. Griffin;H. Tazelaar;C. McGregor
背景和目标。 CTLA-4Ig 与西罗莫司的组合可以促进 CTLA-4Ig 单一疗法无效的同种异体移植模型的无限期生存。我们试图确定 CTLA-4Ig 和西罗莫司的有限疗程是否会改变大鼠原位单肺移植的存活率。方法。将棕色挪威大鼠的左肺移植到四组Lewis受体中（每组n = 6）：第1组，不进行治疗；第2组，mCTLA-4Ig（250μg/天，持续4天）；第3组，西罗莫司（每天3毫克/公斤，持续14天）；第4组，西罗莫司和mCTLA-4Ig联合治疗。通过每日放射学检查确定移植物存活率。在放射学移植物丢失时进行排斥反应的组织学分级以及 T 和 B 淋巴细胞的免疫组织化学染色。结果。第 1 组中出现肺同种异体移植排斥的时间中位数为 6.5 天。西罗莫司和 mCTLA-4Ig 单一疗法均未导致移植物存活时间显着延长（中位生存期分别为 9.5 天和 8.0 天）。与所有其他组相比，第 4 组的移植物存活时间显着延长（中位 29.5 天），并且与所有其他组相比，联合治疗后观察到排斥反应的组织学等级显着降低。对于第 1、2 和 3 组，排斥时 CD8+ve T 细胞的浸润按比例大于 CD4+ve T 细胞的浸润，但联合治疗组则不然。结论。 mCTLA-4Ig 和西罗莫司组合的短期疗程可延长移植物存活，降低排斥反应的严重程度，并减弱完全主要组织相容性复合体不匹配的同种异体肺移植物的 CD8+ve T 细胞浸润。
Background and Aims. The combination of CTLA-4Ig with sirolimus can promote indefinite survival in allograft models for which CTLA-4Ig monotherapy is ineffective. We sought to determine whether a limited course of CTLA-4Ig and sirolimus would alter survival of rat orthotopic single-lung transplantations. Methods. Left lungs of Brown Norway rats were transplanted into four groups of Lewis recipients (n=6 per group): group 1, no treatment; group 2, mCTLA-4Ig (250 &mgr;g/day for 4 days); group 3, sirolimus (3 mg/kg per day for 14 days); group 4, combined therapy with sirolimus and mCTLA-4Ig. Graft survival was determined by daily radiologic examination. Histologic grading of rejection and immunohistochemical staining for T and B lymphocytes were carried out at the time of radiologic graft loss. Results. Rejection of lung allografts in group 1 occurred at a median of 6.5 days. Neither sirolimus nor mCTLA-4Ig monotherapy resulted in significant prolongation of graft survival (median 9.5 and 8.0 days, respectively). Graft survival in group 4 was significantly prolonged compared with all other groups (median 29.5 days), and a significant reduction in histologic grade of rejection was observed following combination therapy compared with all other groups. Infiltration by CD8+ve T cells at the time of rejection was proportionately greater than CD4+ve T-cell infiltration for groups 1, 2, and 3 but not for the combined-therapy group. Conclusions. A brief course of combined mCTLA-4Ig and sirolimus prolongs graft survival, reduces severity of rejection, and attenuates CD8+ve T-cell infiltration of fully major histocompatibility complex mismatched lung allografts.
影响因子：
6.2
作者：
LENSCHOW, DJ;ZENG, YJ;BLUESTONE, JA
通讯作者：
BLUESTONE, JA