Characterization of Sulfamethoxazole and Sulfamethoxazole Metabolite-Specific T-Cell Responses in Animals and Humans

摘要: Sulfamethoxazole (SMX) is associated with hypersensitivity reactions. Identification of drug-specific lymphocytes from hypersensitive patients suggests involvement the immune system. Lymphocytes humans recognize SMX and nitroso-SMX (SMX-NO), whereas cells sensitized rats only SMX-NO. In this investigation, we study nature SMX-specific T in four species. Male rats, mice, rabbits were immunized (50 mg kg –1 ) or SMX-NO (1 ). and/or splenocytes isolated incubated SMX, SMX-hydroxylamine proliferation measured. also SMX-hypersensitive ( n = 3) was addition, bled fortnightly for 4 months to determine whether SMX-NO-specific cross-react SMX. To confirm that responses due covalent binding not cross-reactivity, pulsed coincubated glutathione. Splenocytes proliferated when stimulated SMX-NO, but A 2-h pulse sufficient proliferation, glutathione did proliferate. Rabbit presence SMX-hydroxylamine, converted culture. The SMXNO-specific response rabbit maintained at least Human both metabolites. These results highlight important differences T-cell recognition drug (metabolite) antigens animals have been against a metabolite drug.