title: A new reagent for the induction of T-cell depletion, anti-CD3-CRM9.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Neville
authors.forename: J
authors.initials: J
authors.lastname: Scharff
authors.forename: H Z
authors.initials: HZ
authors.lastname: Hu
authors.forename: K
authors.initials: K
authors.lastname: Rigaut
authors.forename: J
authors.initials: J
authors.lastname: Shiloach
authors.forename: W
authors.initials: W
authors.lastname: Slingerland
authors.forename: M
authors.initials: M
authors.lastname: Jonker
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000992:Antitoxins / Q000096:biosynthesis; D017252:CD3 Complex / Q000276:immunology*; D004167:Diphtheria Toxin / Q000235:genetics / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007202:Indicators and Reagents; D008213:Lymphocyte Activation / Q000187:drug effects*; D008212:Lymphocyte Depletion / Q000379:methods*; D008253:Macaca mulatta; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000992:Antitoxins; D017252:CD3 Complex; D004167:Diphtheria Toxin; D000922:Immunotoxins; D007202:Indicators and Reagents