Characterization of Drug-Specific T Cells in Phenobarbital- Induced Eruption

Abstract

Phenobarbital has a high potential to elicit adverse reactions including severe skin eruptions and systemic involvements among the worldwide-prescribed drugs. Although phenobarbital hypersensitivity is thought to be mediated by T cells specific to the drug, its precise mechanism remains not fully elucidated. To characterize T cells reactive with phenobarbital, we generated drug-specific T cell clones and lines from PBMCs of patients with phenobarbital hypersensitivity showing various degrees of cutaneous and extracutaneous involvements. Although the TCR Vβ repertoire and phenotype in the T cell clones/T cell lines were heterogeneous among the patients, Vβ13.1+ and Vβ5.1+ clones or lines were raised from the individuals examined who possessed different HLA haplotypes. Histopathological examination suggested that Vβ5.1+CD8+ T cells and Vβ13.1+ T cells played a role in cutaneous and extracutaneous involvements, respectively. A Vβ13.1+CD4+ clone was found to proliferate in response to the Ag with processing-impaired, fixed APCs. Most of the clones and lines belonged to the Th2 phenotype, producing IL-4 and IL-5 but not IFN-γ upon phenobarbital stimulation. Clones/lines with Th1 or Th0 phenotypes also constituted minor populations. These observations clearly indicate the heterogeneity and a marked individual deviation of reactive T cell subsets among the patients in terms of CD4/8 phenotype, Vβ repertoire, Ag recognition pattern, and cytokine production; and thus provide evidence whereby each pathogenic T cell subset contributes to special elements of clinical presentation.