title: Cytotoxic mechanisms in different forms of T-cell-mediated drug allergies.
abstract: BACKGROUND
  Cytotoxic mechanisms are involved in different forms of drug induced exanthems.
  
  
  METHODS
  Here we compare the killing pathways of CD4+, CD8+ and CD4/CD8+ T-cell lines (TCL) and clones derived from patients suffering from maculopapular, bullous and pustular drug eruptions. In vitro, perforin and Fas-mediated killing was analysed in cytotoxicity assays against autologous Epstein-Barr virus (EBV)-transformed B-cell lines, Fas-transfected mouse lymphoblasts and natural killer (NK)-target cells. In addition, affected skin lesions and the TCL and clones were stained for perforin and FasL-expression.
  
  
  RESULTS
  We detected perforin and some FasL-mediated killing in all three types of exanthems. Some of the drug-specific T-cell clones analysed exerted mainly perforin-, other more FasL-mediated killing showing no strict relationship between their perforin- and Fas-mediated cytotoxic capacity. Using a cell culture method focusing on the generation of cytotoxic T cells, we detected drug-specific CD8+, TCRalphabeta+ T cells, which failed to proliferate to drug presentation by antigen presenting cells but killed in a drug dependent way. Interestingly, these cells had substantial natural killer-like T cell(s) like features as they were CD56+ and CD94+ and had the ability to kill the NK-sensitive cell line K562.
  
  
  CONCLUSIONS
  Our data underline the important role of cytotoxic mechanisms in different forms of drug induced exanthems and suggest that even some T cells with NK-like characteristics may be involved in drug hypersensitivity.
authors.affiliation: Clinic of Rheumatology and Clinical Immunology/Allergology, PKT 2 D572, Inselspital/University Hospital, CH-3010 Berne, Switzerland.
authors.forename: P C
authors.initials: PC
authors.lastname: Kuechler
authors.forename: M
authors.initials: M
authors.lastname: Britschgi
authors.forename: S
authors.initials: S
authors.lastname: Schmid
authors.forename: Y
authors.initials: Y
authors.lastname: Hari
authors.forename: B
authors.initials: B
authors.lastname: Grabscheid
authors.forename: W J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003875:Drug Eruptions / Q000276:immunology*; D053804:Granzymes; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases