Epitopes described in "Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine."

Article Authors:D Mauri-Hellweg; F Bettens; D Mauri; C Brander; T Hunziker; W J Pichler
Article Title:Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine.
Reference Detail
Reference ID:315060
Abstract:To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonamides and antiepileptics, we analyzed in vitro the drug-induced activation of CD4+ and CD8+ T cell subsets, cytokine secretion, TCR V beta distribution, and proliferation of T cells from four drug-allergic individuals. In addition, the activation parameters CD25 and HLA-DR were analyzed in vivo on CD4+ and CD8+ T cells from five patients with acute drug allergies, some of them with anticonvulsant hypersensitivity syndrome with hepatitis. Our results show that, in vitro, drug-induced proliferation of PBMC from patients with allergy to sulfamethoxazole, 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 secreted high amounts of IL-5 and normal or low levels of IL-2, IFN-gamma, IL-4, and TNF-alpha. An enhanced expansion of TCR V beta 17+ T cells 9 days after in vitro stimulation with sulfamethoxazole was observed in one patient with sulfamethoxazole allergy. The drug specificity of the in vitro-activated T cells was confirmed by generation of different sulfamethoxazole specific T cell lines and CD4+ and CD8+ T cell clones. T cell analysis of patients with acute drug allergy to carbamazepine, phenytoin, allopurinol, or paracetamol confirms the in vitro data, 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.
Reference Type:Literature
PubMed ID:7602118
Journal:J Immunol
Journal Volume:155
Article Pages:462-72
Journal ISSN:0022-1767
Article Chemical List:Anticonvulsants;Cytokines;HLA-DR Antigens;Interleukin-5;Receptors, Antigen, T-Cell, alpha-beta;Receptors, Interleukin-2;Sulfonamides;Carbamazepine;Phenytoin
Article MeSH List:Anticonvulsants(adverse effects); CD4-Positive T-Lymphocytes(immunology); CD8-Positive T-Lymphocytes(immunology); Carbamazepine(adverse effects); Cell Line; Clone Cells; Cytokines(metabolism); Drug Hypersensitivity(etiology); HLA-DR Antigens(physiology); Humans; Interleukin-5(biosynthesis); Lymphocyte Activation(immunology); Lymphocytes(metabolism); Phenytoin(adverse effects); Receptors, Antigen, T-Cell, alpha-beta(immunology); Receptors, Interleukin-2(physiology); Sulfonamides(adverse effects)
Article Comments:Data originally imported from the Database of Functional Molecular Immunology, FIMM (http://sdmc.lit.org.sg:8080/fimm/)
Curation Last Updated:2016-05-11 20:01:33