Immunosuppressive antimetabolites inhibit induction of contact hypersensitivity while lymphoablative drugs also prevent its expression.
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.
Quéméneur
Laurence
L
Laboratory of immunopharmacology, INSERM U503, Claude Bernard University, 21, avenue T. Garnier, 69365 Lyon, France.
Michallet
Marie-Cécile
MC
Ferraro-Peyret
Carole
C
Saint-Mézard
Pierre
P
Benetière
Josette
J
Ducluzeau
Marie-Thérèse
MT
Nicolas
Jean-François
JF
Revillard
Jean-Pierre
JP
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
D000963:Antimetabolites; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D008942:Mitoxantrone; D004139:Dinitrofluorobenzene; D009173:Mycophenolic Acid; D005472:Fluorouracil; D008727:Methotrexate