Neville D M, Scharff J, Hu H Z, Rigaut K, Shiloach J, Slingerland W, Jonker M
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034, USA.
J Immunother Emphasis Tumor Immunol. 1996 Mar;19(2):85-92. doi: 10.1097/00002371-199603000-00001.
We have developed a new reagent for inducing in vivo T-cell depletion and have tested this reagent in rhesus monkeys. The reagent is an anti-CD3 epsilon immunotoxin based on a diphtheria toxin binding-site mutant, CRM9. After administration to monkeys, T cells are depleted from both the blood and lymph node compartments to < 1% of their initial values. T-cell depletion is associated with transient immunosuppression, as judged by delayed rejection of RhLA-mismatched skin allografts. T cells are repopulated in both compartments; however, the rate of repopulation is age dependent. The rate is rapid in juvenile animals (12 days) and requires > 30 days in old animals. The correlation between repopulation rate and age suggests that the repopulation is thymus dependent and that the repopulated T cells are probably naive T cells. This reagent should be a valuable tool in studying the role of memory T cells in rhesus models of autoimmune diseases and protocols of tolerance induction after organ transplantation.
我们研发了一种用于体内诱导T细胞耗竭的新型试剂，并在恒河猴身上对该试剂进行了测试。该试剂是一种基于白喉毒素结合位点突变体CRM9的抗CD3ε免疫毒素。给猴子注射后，血液和淋巴结中的T细胞均减少至初始值的<1%。从RhLA不匹配皮肤同种异体移植物的延迟排斥反应判断，T细胞耗竭与短暂的免疫抑制有关。两个部位的T细胞都重新增殖；然而，重新增殖的速度与年龄有关。幼年动物（12天）的重新增殖速度很快，而老年动物则需要>30天。重新增殖速度与年龄之间的相关性表明，重新增殖依赖于胸腺，重新增殖的T细胞可能是初始T细胞。这种试剂在研究记忆T细胞在恒河猴自身免疫性疾病模型中的作用以及器官移植后耐受诱导方案方面应是一种有价值的工具。
