A NEW REAGENT FOR THE INDUCTION OF T-CELL DEPLETION, ANTI-CD3-CRM9

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, CRM 9. After administration to monkeys, T cells are depleted from both the blood and lymph node compartments to <1% of their initial values. T-c ell depletion is associated with transient immunosuppression, as judge d by delayed rejection of RhLA-mismatched skin allografts. T cells are repopulated in both compartments; however, the rate of repopulation i s age dependent. The rate is rapid in juvenile animals (12 days) and r equires >30 days in old animals. The correlation between repopulation rate and age suggests that the repopulation is thymus dependent and th at the repopulated T cells are probably naive T cells. This reagent sh ould be a valuable tool in studying the role of memory T cells in rhes us models of autoimmune diseases and protocols of tolerance induction after organ transplantation.