Garrovillo M, Ali A, Depaz H A, Gopinathan R, Oluwole O O, Hardy M A, Oluwole S F
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Am J Transplant. 2001 Jul;1(2):129-37.
We have studied the effects of adoptive transfer of host thymic dendritic cells pulsed with immunodominant WF Class I peptide 5 (residues 93-109) on cardiac allograft survival in the WF-to-ACI rat combination. Our results showed that, whereas intrathymic inoculation of WF peptide 5-pulsed ACI thymic dendritic cells alone on day -7 did not prolong graft survival, similar treatment combined with 0.5 mL antilymphocyte serum (ALS) led to 100% permanent acceptance (> 200d) of donor-specific cardiac allografts. Extension of our study to systemic administration of peptide 5-pulsed host thymic dendritic cells confirmed that intravenous injection of peptide 5-pulsed self thymic dendritic cells combined with ALS transient immunosuppression resulted in 100% permanent donor-specific graft survival (> 200d). These results were reproducible in a clinically relevant model using intravenous injection of peptide-pulsed host myeloid dendritic cells. In contrast, thymectomy prior to adoptive transfer of peptide-pulsed host dendritic cells resulted in acute graft rejection at times equivalent to rejection in thymectomized controls. The long-term unresponsive recipients challenged with second-set grafts accepted permanently (> 100d) donor-type (WF) but not third party (Lewis) cardiac allografts. This study suggests that intravenous administration of genetically engineered dendritic cells expressing donor MHC molecules has the potential of inducing transplant tolerance.
我们研究了用免疫显性WF I类肽5（第93 - 109位氨基酸残基）脉冲处理的宿主胸腺树突状细胞过继转移对WF品系大鼠至ACI品系大鼠心脏同种异体移植存活的影响。我们的结果显示，虽然在第-7天单独进行胸腺内接种经WF肽5脉冲处理的ACI胸腺树突状细胞并未延长移植物存活时间，但类似处理联合0.5 mL抗淋巴细胞血清（ALS）导致供体特异性心脏同种异体移植物100%永久存活（> 200天）。将我们的研究扩展至经肽5脉冲处理的宿主胸腺树突状细胞的全身给药，证实静脉注射经肽5脉冲处理的自身胸腺树突状细胞联合ALS短暂免疫抑制可导致100%供体特异性移植物永久存活（> 200天）。这些结果在用静脉注射经肽脉冲处理的宿主髓样树突状细胞的临床相关模型中是可重复的。相比之下，在经肽脉冲处理的宿主树突状细胞过继转移之前进行胸腺切除导致急性移植物排斥，其时间与胸腺切除对照中的排斥时间相当。用二次移植挑战长期无反应的受体，其永久接受（> 100天）供体型（WF）但不接受第三方（Lewis）心脏同种异体移植物。本研究表明，静脉注射表达供体MHC分子的基因工程树突状细胞具有诱导移植耐受的潜力。
