A new reagent for the induction of T-cell depletion, anti-CD3-CRM9

被引:70
作者
Neville, DM
Scharff, J
Hu, HZ
Rigaut, K
Shiloach, J
Slingerland, W
Jonker, M
机构
[1] NIDDK, BIOTECHNOL UNIT, CELLULAR & DEV BIOL LAB, NIH, BETHESDA, MD USA
[2] BIOMED PRIMATE RES CTR, RIJSWIJK, NETHERLANDS
关键词
immunotoxin; TCR; CD3; epsilon; rhesus; transplantation; autoimmune;
D O I
10.1097/00002371-199603000-00001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-CDSE 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.
引用
收藏
页码:85 / 92
页数:8
相关论文
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