PREVENTION OF ALLOANTIBODY FORMATION AFTER SKIN-GRAFTING WITHOUT PROLONGATION OF GRAFT-SURVIVAL BY ANTI-L3T4 INVIVO
PREVENTION OF ALLOANTIBODY FORMATION AFTER SKIN-GRAFTING WITHOUT PROLONGATION OF GRAFT-SURVIVAL BY ANTI-L3T4 INVIVO
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DOI：
10.1097/00007890-198806000-00024
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发表时间：
1988-06-01
期刊：
影响因子：
6.2
通讯作者：
WINN, HJ
中科院分区：
文献类型：
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作者：
AUCHINCLOSS, H;GHOBRIAL, RRM;WINN, HJ
用抗L3 T4抗原（人类中的CD 4）的单克隆抗体在体内治疗小鼠，已显示抑制对几种外源抗原的体液应答，并在某些情况下延长同种异体移植物的存活。因此，进行实验以测试抗L3 T4抗体治疗是否会抑制皮肤移植后的同种抗体产生。在BALB/c皮肤移植前，将单克隆抗L3 T4抗体（GK 1.5）给予C57 BL/6（B6）小鼠。 在移植排斥反应后检测B6抗BALB/c同种抗体的产生。结果表明：（1）抗L_3T_4处理不能显著延长BALB/c小鼠皮肤移植物的存活时间，（2）同时用抗L_3T_4和抗Lyt_2抗体处理能显著延长移植物的存活时间，（3）抗L_3T_4处理能减少移植后同种抗体的产生，如果同时进行胸腺切除则能完全消除同种抗体的产生。（4）胸腺切除延长了抗L_3T_4治疗的有效性：（5）对抗L_3T_4治疗时呈递的同种抗原不能产生耐受;和（6）即使同时进行抗L3 T4治疗，在二次移植后，已确定的细胞毒性抗体滴度也上升到更高水平，而弱抗体滴度保持稳定或降低。这些结果表明，L3 T4+细胞在提供产生对同种异体抗原的体液应答所必需的“帮助”方面是必不可少的，但是这些L3 T4+细胞的消除仍然允许产生对细胞介导的免疫的帮助。数据还表明，I类抗原必须呈递在II类分子上，以引发抗体应答。
Treatment of mice in vivo with monoclonal antibodies against the L3T4 antigen (CD4 in human beings) has been shown to suppress the humoral response to several foreign antigens and to prolong the survival of allografts in some cases. Experiments were therefore performed to test whether anti-L3T4 antibody treatment would suppress alloantibody production after skin transplantation. Monoclonal anti-L3T4 antibody (GK1.5) was administered to C57BL/6 (B6) mice prior to BALB/c skin grafting. The production of B6 anti-BALB/c alloantibody was then tested after graft rejection. The results showed that: (1) graft survival of BALB/c skin on B6 mice was not substantially prolonged by anti-L3T4 treatment; (2) graft survival was significantly prolonged if mice were treated with both anti-L3T4 and anti-Lyt2 antibody; (3) the production of alloantibody following grafting was decreased by anti-L3T4 treatment and was completely eliminated if thymectomy was also performed; (4) thymectomy prolonged the effectiveness of the anti-L3T4 treatment; (5) tolerance to alloantigens presented at the time of anti-L3T4 treatment was not achieved; and (6) well-established cytotoxic antibody titers rose to higher levels after secondary grafting even with concurrent anti-L3T4 treatment, while weak antibody titers remained stable or decreased. These results indicate that L3T4+ cells are essential in providing the "help" necessary for generating humoral responses to alloantigens but that elimination of these L3T4+ cells still allows the generation of help for cell-mediated immunity. The data also suggest that class I antigens must be presented on class II molecules in order to elicit an antibody response.