Cryopreserved-skin grafting in Rats under administration of anti-CD2 menochlonal antibody

前言：免疫抑制剂用于心、肺、肝、肾等重要器官的同种异体移植已被广泛接受。然而，这些药物确实有副作用，很难证明将这些药物用于转移其他非重要器官或组织是合理的。不使用这些药物的组织移植的发展将扩大非重要器官或组织的适应症，用于严重创伤或恶性肿瘤切除后复杂缺损的重建。材料和方法：采用刘易斯（LEW）和Brown Norway（BN）大鼠严重错配模型，应用抗CD 2单克隆抗体（mAb）进行同种异体皮肤移植。用培养的杂交瘤细胞（OX 34）腹腔注射小鼠制备大鼠抗CD 2单克隆抗体。通过流式细胞术确定产生的抗体的有效剂量为2 mg/kg。B成功地进行了两例BN大鼠至LEW大鼠的异位心脏移植 ...更多信息 术前、术后两次给予相同剂量的抗体。将BN大鼠的全层腹部皮肤（2片1.5 × 2cm皮肤）移植到LEW的背部。A组（12只移植物）：对照组B（12只移植物）：从移植前2天开始，连续2天腹腔注射抗CD 2单抗2 mg/kg。C组（12只）：移植前1天开始连续9天注射相同剂量的注射液。以PVG为第三方进行混合淋巴细胞反应试验，评价受体大鼠的淋巴细胞功能。结果：未治疗组和治疗2 d组大鼠的皮片在术后10 d内均发生排斥反应。与此相反，治疗9天的大鼠移植皮肤存活超过20天（平均存活期：51天，最长：98天）。混合淋巴细胞反应试验显示，A组对BN的反应强于PVG，B组对BN和PVG的反应相似，表明单克隆抗体给药后2周淋巴细胞功能恢复。在C组中，BN和PVG的反应是小于在A组或B和PVG的反应显着更强，表明更广泛的抑制淋巴细胞功能2周后，9个连续给药mAbs.Discussion：这份报告表明，抗CD 2单克隆抗体治疗可以显着延迟排斥反应的异体皮肤移植在主要不匹配的大鼠模型。考虑到异体皮肤移植的困难，使用抗CD 2单克隆抗体的其他异体组织移植用于全肢、关节或神经可能会更成功。少

Introduction : It is well accepted to use immuno-suppressing agents for the allografting of the important organs such as heart, lung, liver or kidney. However, these agents do have side effects and it is difficult to justify to use these drugs for the transfer of other non-vital organs or tissues. Development of tissue transfer without using these agents would extend indications for non-vital organs or tissues for the reconstruction of complicated defect after sever trauma or malignant tumor resection. We used anti-CD2 monoclonal antibodies (mAbs) for allo-skin grafting in rat major mismatch model.Materials and Metods : Major mismatch model of Lewis (LEW) and Brown Norway (BN) rats was used. Rat anti-CD2 monoclonal antibiesantibodies was made by intra-peritoneal injection of cultured hybridoma cell (OX34) to mouse. The effective dose of created antibodies was determined as 2 mg/kg by flow-cytometry. Two successful heterotopic heart transplantation from BN to LEW rat were demonstrated b … More y the twice administration of the same dose antibodies before and after surgery. Full thickness abdominal skin (2 sheets of 1.5x2 cm skin) of BN rats was grafted onto the back of LEW.Three groups were created. Group A (12 grafts) : control Group B (12 grafts) : Anti-CD2 mAbs of 2 mg/kg were injected intraperitoneally to LEW rats for 2 consecutive days beginning two days before grafting. Group C (12 grafts) : same dose injection for 9 consecutive days beginning one day before grafting. Mixed lymphocyte reaction test using PVG as the third party was performed to evaluate lymphocyte function of the recipient rat.Results : Skin grafts of untreated rats or those of 2 day treated rats were all rejected within 10 days postoperatively. In contrast, grafted skin of rats treated for 9 days survived for than 20 days (mean survival period : 51 days, longest : 98 days). Mixed lymphocyte reaction test showed that group A demonstrated more reaction to BN than PVG and group B showed similar strong reaction to both BN and PVG suggesting recovery of lymphocyte function 2 weeks after mAbs administration. In group C,reaction to BN and PVG was less than that in group A or B and significantly stronger reaction to PVG suggesting more generalized suppression to lymphocyte function 2 weeks after 9 consecutive administration of mAbs.Discussion : This report shows that anti-CD2 monoclonal antibody treatment may significantly delay rejection of allo-skin grafting in major mismatched rat model. Considering the difficulty in allo-skin grafting, other allo-tissue transfer using anti-CD2 monoclonal antibodies for total limb, joint or nerve may be more successful. Less