HIGH IL-5 PRODUCTION BY HUMAN DRUG-SPECIFIC CELL CLONES

To analyze whether and how T cells are involved in drug allergies, we analyzed the drug-induced activation of T cell subsets, T cell recepto r V-beta usage and cytokine secretion of T cells from the peripheral b lood of drug-allergic individuals. The specificity of the T cells was demonstrated by specific restimulation of drug specific clones. We fou nd that drugs which do not need to be metabolized to become immunogeni c (haptens like penicillin G) can stimulate CD4+ and CD8+ T cells in v itro. The T cell response to penicillin can be oligoclonal (use of a c ertain T cell receptor V beta only) or polyclonal. Only polyclonal T c ell lines were cross-reactive with other beta-lactam antibiotics. Sulf amethoxazole and lidocaine are thought to gain their ability to bind t o proteins by intracellular drug metabolism. They were found to stimul ate CD4+ and CD8+ T cells in vitro, and some reactive T cell lines wer e oligoclonal. The majority of lidocaine-specific clones secreted rath er high amounts of IL-5 and IL-4 after PMA/ionomycin stimulations (Th2 -like), but some CD4+ and all CD8+ clones had a Th1-like phenotype (hi gh INF-gamma and TNF-alpha). The data clearly demonstrate the existenc e of drug-specific alpha beta+ T cells in the circulation of drug-alle rgic individuals and reveal a great heterogeneity of T-cell-mediated r esponses. Further studies are needed to correlate the type of T cell r esponse to the clinical picture, which can be quite heterogeneous.