Regulatory cell-mediated tolerance does not protect against chronic rejection

Regulatory cell-mediated tolerance does not protect against chronic rejection
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DOI:
10.1097/01.tp.0000080980.26287.11
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发表时间:
2003-08-15
期刊:
影响因子:
6.2
通讯作者:
Pirenne, J
Pirenne, J
中科院分区:
医学2区
文献类型:
--
作者:
Koshiba, T;Kitade, H;Pirenne, J

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背景调节性细胞可能通过促进Th 2偏移来防止移植物丧失至急性排斥并诱导耐受。Th 2细胞因子刺激B细胞,其引起同种抗体介导的慢性排斥。我们试图确定调节性细胞介导的耐受性是否能防止慢性排斥反应。以RA(RT 1(P))和PVG(RT 1(c))大鼠为供体和受体进行心脏移植(Htx)。在preTx第12天给予供体特异性输血(DSBT)。在第100天植入二级移植物。将脾细胞从耐受大鼠(和对照)转移到轻度照射(450 rad)的幼稚PVG中,其接受RA Htx。研究原发性Htx的血管闭塞(VO)的发展、Th 1/Th 2的产生、移植物内细胞因子、移植物浸润的性质以及免疫球蛋白(IG)G同种型和补体(C3)结合的内皮沉积。结果RA Htx在10天内被拒绝(8,9,10 x4)。PreTx DSBT无限期延长原发性Htx存活时间(>140天),接受第二供体特异性(但不是第三方)移植物(P
Background. Regulatory cells prevent graft loss to acute rejection and induce tolerance, possibly by promoting Th2 deviation. Th2 cytokines stimulate B cells, which cause alloantibody-mediated chronic rejection. We searched to determine whether regulatory cell-mediated tolerance protects or not against chronic rejection.Methods. Heart transplantation (Htx) was performed using RA (RT1(P)) and PVG (RT1(c)) rats as donor and recipients. Donor-specific blood transfusion (DSBT) was given on preTx day 12. Secondary grafts were implanted at day 100. Splenocytes were transferred from tolerant rats (and controls) into lightly irradiated (450 rad) naive PVG, which received RA Htx. Primary Htx were investigated for the development of vascular occlusion (VO), the production of Th1/Th2, intragraft cytokines, and for the nature of graft infiltrate as well as for endothelial deposition of immunoglobulin (Ig)G isotypes and complement (C3) binding.Results were compared with rejecting controls (no DSBT) and syngeneic Htx. Results. RA Htx were rejected within 10 days (8, 9, 10x4). PreTx DSBT prolonged primary Htx survival indefinitely (>140 days) with acceptance of secondary donor-specific (but not third-party) grafts (P