title: Immunosuppressive antimetabolites inhibit induction of contact hypersensitivity while lymphoablative drugs also prevent its expression.
abstract: Contact hypersensitivity is one of the most common skin diseases and its pharmacological control is an important clinical issue. We investigated the control of contact hypersensitivity by immunosuppressive drugs administered during sensitization or challenge. Mycophenolate mofetil, methotrexate and 5-fluorouracil completely inhibited contact hypersensitivity when administered during sensitization whereas they did not decrease inflammatory reaction when administered during challenge. Conversely, mitoxantrone, and cyclophosphamide, given as a single injection at the time of sensitization or challenge, completely inhibited the reaction, a property associated with T and B cell depletion. The data indicate that antimetabolites which are cell cycle dependent inhibit clonal expansion and subsequent differentiation of cytotoxic CD8+ T cells. Their lack of effect at the time of challenge indicates that T cell proliferation is not required for the expression of effector or regulatory T cell activation. Conversely lymphoablative drugs can inactivate or destroy differentiated cytotoxic T cells with rapid kinetics.
authors.affiliation: Laboratory of immunopharmacology, INSERM U503, Claude Bernard University, 21, avenue T. Garnier, 69365 Lyon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Quéméneur
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Michallet
authors.forename: Carole
authors.initials: C
authors.lastname: Ferraro-Peyret
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Mézard
authors.forename: Josette
authors.initials: J
authors.lastname: Benetière
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Ducluzeau
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Nicolas
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Revillard
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000517:prevention & control; D004139:Dinitrofluorobenzene; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects*; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008942:Mitoxantrone / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D008942:Mitoxantrone; D004139:Dinitrofluorobenzene; D009173:Mycophenolic Acid; D005472:Fluorouracil; D008727:Methotrexate