@article {Naisbitt732, author = {D. J. Naisbitt and M. Britschgi and G. Wong and J. Farrell and J. P. H. Depta and D. W. Chadwick and W. J. Pichler and M. Pirmohamed and B. K. Park}, title = {Hypersensitivity Reactions to Carbamazepine: Characterization of the Specificity, Phenotype, and Cytokine Profile of Drug-Specific T Cell Clones}, volume = {63}, number = {3}, pages = {732--741}, year = {2003}, doi = {10.1124/mol.63.3.732}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Administration of carbamazepine (CBZ) causes hypersensitivity reactions clinically characterized by skin involvement, eosinophilia, and systemic symptoms. These reactions have an immune etiology; however, the role of T cells is not well defined. The aim of this study was to characterize the specificity, phenotype, and cytokine profile of CBZ-specific T cells derived from hypersensitive individuals. Proliferation of blood lymphocytes was measured using the lymphocyte transformation test. CBZ-specific T cell clones were generated by serial dilution and characterized in terms of their cluster of differentiation and T cell receptor Vβ phenotype. Proliferation, cytotoxicity, and cytokine secretion were measured by [3H]thymidine incorporation, 51Cr release, and enzyme-linked immunosorbent assay, respectively. HLA blocking antibodies were used to study the involvement of antigen-presenting cells. The specificity of the drug T cell receptor interaction was studied using CBZ metabolites and other structurally related compounds. Lymphocytes from hypersensitive patients (stimulation index: 32.1 {\textpm} 24.2 [10 μg ml-1]) but not control patients (stimulation index: 1.2 {\textpm} 0.4 [10 μg ml-1]) proliferated upon stimulation with CBZ. Of 44 CBZ-specific T cell clones generated, 10 were selected for further analysis. All 10 clones were either CD4+ or CD4+/CD8+, expressed the αβ T cell receptor, secreted IFN-γ, and were cytotoxic. T-cell recognition of CBZ was dependent on the presence of HLA class II (DR/DQ)-matched antigen-presenting cells. The T cell receptor of certain clones could accommodate some CBZ metabolites, but no cross-reactivity was seen with other anticonvulsants or structural analogs. These studies characterize drug-specific T cells in CBZ-hypersensitive patients that are phenotypically different from T cells involved in other serious cutaneous adverse drug reactions.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/63/3/732}, eprint = {https://molpharm.aspetjournals.org/content/63/3/732.full.pdf}, journal = {Molecular Pharmacology} }