title: Depletion of T lymphocytes with immunotoxin retards the progress of experimental allergic encephalomyelitis in rhesus monkeys.
abstract: FN18-CRM9 is an anti-rhesus anti-CD3 immunotoxin that can transiently deplete T cells to 1% of initial values in both the blood and lymph node compartments and can induce long-term tolerance to mismatched renal allografts. We have investigated the ability of this immunotoxin to interdict the course of an experimental rhesus T-cell-driven autoimmune disease, experimental allergic encephalomyelitis (EAE) induced by myelin basic protein. Monkeys showing CSF pleocytosis were then treated with FN18-CRM9 alone or in combination with cranial irradiation (325 or 650 cGy). EAE in nontreated control monkeys progressed rapidly. Paralysis occurred 4-6 days after CSF pleocytosis. Paralysis was either delayed or never occurred in treated monkeys, and histopathology revealed few inflammatory plaques that were notable for their low or absent T cell content. While T cells repopulate in the periphery posttreatment, they do not return to the CNS in large numbers, suggesting that the newly repopulated T cells have lost their previously acquired CNS homing capability. Anti-CD3 immunotoxin may be useful in treating clinical T-cell-driven autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 28092-4034, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.forename: S
authors.initials: S
authors.lastname: Stavrou
authors.forename: B
authors.initials: B
authors.lastname: Cairns Baker
authors.forename: C
authors.initials: C
authors.lastname: Tornatore
authors.forename: J
authors.initials: J
authors.lastname: Scharff
authors.forename: P
authors.initials: P
authors.lastname: Okunieff
authors.forename: D M
authors.initials: DM
authors.lastname: Neville
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000494:pharmacology*; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D004676:Myelin Basic Protein / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D017252:CD3 Complex; D000922:Immunotoxins; D004676:Myelin Basic Protein