title: T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity.
abstract: BACKGROUND
  Quinolones are widely used, broad spectrum antibiotics that can induce immediate- and delayed-type hypersensitivity reactions, presumably either IgE or T cell mediated, in about 2-3% of treated patients.
  
  
  OBJECTIVE
  To better understand how T cells interact with quinolones, we analysed six patients with delayed hypersensitivity reactions to ciprofloxacin (CPFX), norfloxacin (NRFX) or moxifloxacin (MXFX).
  
  
  METHODS
  We confirmed the involvement of T cells in vivo by patch test and in vitro by means of the lymphocyte proliferation test (LTT). The nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones were investigated through the generation and analysis (flow cytometry and proliferation assays) of quinolone-specific T cell clones (TCC).
  
  
  RESULTS
  The LTT confirmed the involvement of T cells because peripheral blood mononuclear cells (PBMC) mounted an enhanced in vitro proliferative response to CPFX and/or NRFX or MXFX in all patients. Patch tests were positive after 24 and 48 h in three out of the six patients. From two patients, CPFX- and MXFX-specific CD4(+)/CD8(+) T cell receptor (TCR) alphabeta(+) TCC were generated to investigate the nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones. The use of eight different quinolones as antigens (Ag) revealed three patterns of cross-reactivity: clones exclusively reacting with the eliciting drug, clones with a limited cross-reactivity and clones showing a broad cross-reactivity. The TCC recognized quinolones directly without need of processing and without covalent association with the major histocompatability complex (MHC)-peptide complex, as glutaraldehyde-fixed Ag-presenting cells (APC) could present the drug and washing quinolone-pulsed APC removed the drug, abrogating the reactivity of quinolone-specific TCC.
  
  
  CONCLUSIONS
  Our data show that T cells are involved in delayed immune reactions to quinolones and that cross-reactivity among the different quinolones is frequent.
authors.affiliation: Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, University of Bern, Bern, Switzerland.
authors.forename: D A
authors.initials: DA
authors.lastname: Schmid
authors.forename: J P H
authors.initials: JP
authors.lastname: Depta
authors.forename: W J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000737:chemistry / Q000494:pharmacology; D002999:Clone Cells; D003429:Cross Reactions; D004342:Drug Hypersensitivity / Q000276:immunology*; D015365:Enoxacin / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008875:Middle Aged; D000077266:Moxifloxacin; D009268:Nalidixic Acid / Q000737:chemistry / Q000494:pharmacology; D009643:Norfloxacin / Q000737:chemistry / Q000494:pharmacology; D015242:Ofloxacin / Q000737:chemistry / Q000494:pharmacology; D010328:Patch Tests; D010876:Pipemidic Acid / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D015363:Quinolones; D015365:Enoxacin; D009268:Nalidixic Acid; D002939:Ciprofloxacin; D015242:Ofloxacin; C053091:lomefloxacin; D010876:Pipemidic Acid; D009643:Norfloxacin; D000077266:Moxifloxacin