Characterization of drug-specific T cells in phenobarbital-induced eruption.
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 Vbeta repertoire and phenotype in the T cell clones/T cell lines were heterogeneous among the patients, Vbeta13.1(+) and Vbeta5.1(+) clones or lines were raised from the individuals examined who possessed different HLA haplotypes. Histopathological examination suggested that Vbeta5.1(+)CD8(+) T cells and Vbeta13.1(+) T cells played a role in cutaneous and extracutaneous involvements, respectively. A Vbeta13.1(+)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-gamma 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, Vbeta repertoire, Ag recognition pattern, and cytokine production; and thus provide evidence whereby each pathogenic T cell subset contributes to special elements of clinical presentation.
Hashizume
Hideo
H
Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Hamamatsu 431-3192, Japan. hihashiz@hama-med.ac.jp
Takigawa
Masahiro
M
Tokura
Yoshiki
Y
D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000187:drug effects; D015704:CD4 Antigens / Q000096:biosynthesis; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002675:Child, Preschool; D002999:Clone Cells; D003875:Drug Eruptions / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000187:drug effects; D006239:Haplotypes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000096:biosynthesis; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex / Q000187:drug effects / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000009:adverse effects* / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010634:Phenobarbital