High IL-5 Production by Human Drug-Specific T Cell Clones

Abstract

To analyze whether and how T cells are involved in drug allergies, we analyzed the drug-induced activation of T cell subsets, T cell receptor V-β usage and cytokine secretion of T cells from the peripheral blood of drug-allergic individuals. The specificity of the T cells was demonstrated by specific restimulation of drug specific clones. We found that drugs which do not need to be metabolized to become immunogenic (haptens like penicillin G) can stimulate CD4+ and CD8+ T cells in vitro. The T cell response to penicillin can be oligoclonal (use of a certain T cell receptor Vβ only) or polyclonal. Only polyclonal T cell lines were cross-reactive with other β-lactam antibiotics. Sulfamethoxazole and lidocaine are thought to gain their ability to bind to proteins by intracellular drug metabolism. They were found to stimulate CD4+ and CD8+ T cells in vitro, and some reactive T cell lines were oligoclonal. The majority of lidocaine-specific clones secreted rather 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 (high INF-γ and TNF-α). The data clearly demonstrate the existence of drug-specific αβ+ T cells in the circulation of drug-allergic individuals and reveal a great heterogeneity of T-cell-mediated responses. Further studies are needed to correlate the type of T cell response to the clinical picture, which can be quite heterogeneous.

Mass Spectrometric Characterization of Circulating and Functional Antigens Derived from Piperacillin in Patients with Cystic Fibrosis

“…The cytokine profile associated with a particular reaction determines the nature of the induced immune response (1, 38-42). Ag (43,44), was not seen in piperacillin-hypersensitive patients, and this may relate to the absence of eosinophilia as a clinical feature. The detection of IL-1b, TNF-a, and IL-6 in culture supernatant containing piperacillin-stimulated PBMCs from hypersensitive patients and tolerant controls (albeit to a lesser extent) are suggestive of a dendritic cell response against piperacillin, as has recently been described with amoxicillin (45,46).…”

Drug Antigenicity, Immunogenicity, and Costimulatory Signaling: Evidence for Formation of a Functional Antigen through Immune Cell Metabolism

“…Previous studies using lymphocytes from SMX-hypersensitive patients and animal models of SMX immunogenicity demonstrated that Ag-stimulated T cells secrete high levels of the Th2 cytokine IL-5 and the Th1 cytokine IFN-g (41,47,48). Data presented in the current study using multiplex methods and cloned T cells confirm these initial reports.…”

CD1d-restricted T cell activation by nonlipidic small molecules

“…Our study shows that such nonlipidic small molecules can be recognized in association with CD1d proteins by describing human ␣␤ T cells that are selectively activated by PPBF and structurally related compounds. PPBFs are synthetic rather than environmental antigens, but they share chemical features with commonly used sulfa drugs that generate strong hypersensitivity reactions in humans, including sulfisomidine, sulfadiazine, sulfasalazine, and celecoxib (45). Current studies are looking into the possibility that these antibiotics and antiinflammatory drugs may also be CD1-restricted antigens.…”