ACTIVATION OF DRUG-SPECIFIC CD4(-CELLS IN INDIVIDUALS ALLERGIC TO SULFONAMIDES, PHENYTOIN, AND CARBAMAZEPINE() AND CD8(+) T)

To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonami des and antiepileptics, we analyzed in vitro the drug-induced activati on of CD4(+) and CD8(+) T cell subsets, cytokine secretion, TCR V beta distribution, and proliferation of T cells from four drug-allergic in dividuals. In addition, the activation parameters CD25 and HLA-DR were analyzed in vive on CD4(+) and CD8(+) T cells from five patients with acute drug allergies, some of them with anticonvulsant hypersensitivi ty syndrome with hepatitis. Our results show that, in vitro, drug-indu ced proliferation of PBMC from patients with allergy to sulfamethoxazo le, phenytoin, or carbamazepine was specific and dose dependent. CD4() as well as CD8(+) T cells expressed elevated levels of CD25 and HLA- DR molecules after drug stimulation. Drug-activated lymphocytes secret ed high amounts of IL-5 and normal or low levels of IL-2, IFN-gamma, I L-4, and TNF-alpha. An enhanced expansion of TCR V beta 17(+) T cells 9 days after in vitro stimulation with sulfamethoxazole was observed i n one patient with sulfamethoxazole allergy. The drug specificity of t he in vitro-activated T cells was confirmed by generation of different sulfamethoxazole specific T cell lines and CD4(+) and CD8(+) T cell c lones. T cell analysis of patients with acute drug allergy to carbamaz epine, phenytoin, allopurinol, or paracetamol confirms the in vitro da ta, because all patients had activated CD4(+) or CD8(+) T cells in the circulation. Our data clearly show the involvement of drug-specific T cells in drug allergies.