title: CD69 upregulation on T cells as an in vitro marker for delayed-type drug hypersensitivity.
abstract: BACKGROUND
  T cells play a key role in delayed-type drug hypersensitivity reactions. Their reactivity can be assessed by their proliferation in response to the drug in the lymphocyte transformation test (LTT). However, the LTT imposes limitations in terms of practicability, and an alternative method that is easier to implement than the LTT would be desirable.
  
  
  METHODS
  Four months to 12 years after acute drug hypersensitivity reactions, CD69 upregulation on T cells of 15 patients and five healthy controls was analyzed by flow cytometry.
  
  
  RESULTS
  All 15 LTT-positive patients showed a significant increase of CD69 expression on T cells after 48 h of drug-stimulation exclusively with the drugs incriminated in drug-hypersensitivities. A stimulation index of 2 as cut-off value allowed discrimination between nonreactive and reactive T cells in LTT and CD69 upregulation. T cells (0.5-3%) showed CD69 up-regulation. The reactive cell population consisted of a minority of truly drug reactive T cells secreting cytokines and a higher number of bystander T cells activated by IL-2 and possibly other cytokines.
  
  
  CONCLUSIONS
  CD69 upregulation was observed after 2 days in all patients with a positive LTT after 6 days, thus appearing to be a promising tool to identify drug-reactive T cells in the peripheral blood of patients with drug-hypersensitivity reactions.
authors.affiliation: Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, Bern, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Beeler
authors.forename: L
authors.initials: L
authors.lastname: Zaccaria
authors.forename: T
authors.initials: T
authors.lastname: Kawabata
authors.forename: B O
authors.initials: BO
authors.lastname: Gerber
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 / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D000099192:CD69 Antigens
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D037181:Lectins, C-Type; D000099192:CD69 Antigens