title: The lipophilic hapten parthenolide induces interferon-gamma and interleukin-13 production by peripheral blood-derived CD8+ T cells from contact allergic subjects in vitro.
abstract: BACKGROUND
  Peripheral blood mononuclear cells (PBMC) from persons with contact allergy to nickel react in vitro predominantly with nickel-induced CD4+ T cell-mediated production of both T-cell type 1 and 2 cytokines.
  
  
  OBJECTIVE
  The aim of the present study was to investigate if the contact allergen parthenolide, a sesquiterpene lactone of lipophilic character, elicits an immune response which differs from that induced by water-soluble nickel ions.
  
  
  METHODS
  Ten allergic subjects with strong (n = 6), moderate (n = 2), or weak (n = 2) patch-test reactivity to parthenolide and five patch test-negative control subjects participated in the study. PBMC from the subjects were analysed for in vitro reactivity with parthenolide by an enzyme-linked immunospot (ELISpot) assay, measuring cytokine production at the single-cell level.
  
  
  RESULTS
  The allergic group, but not the control group, responded to parthenolide with increased numbers of cells producing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-5 (P < 0.05 for all) and IL-13 (P < 0.01). The responses manifested by T-cell type 1 (IFN-gamma and IL-2) and type 2 (IL-4, IL-5 and IL-13) cytokines were positively correlated between cytokines. Subjects with a strong or moderate, but not weak or negative, patch-test reaction displayed detectable in vitro responses. In contrast to the CD4+ T cell-mediated peripheral reactivity induced by nickel, cell depletion experiments identified the parthenolide-reactive IFN-gamma- and IL-13-producing cells as CD8+ T cells.
  
  
  CONCLUSIONS
  The finding that the PBMC reactivity to parthenolide in humans involves a CD8+ T cell-mediated type 1 and 2 cytokine response warrants further studies on the relationship between the chemical nature of a hapten and the resulting immune response.
authors.affiliation: Mabtech, Nacka Strand, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Wahlkvist
authors.forename: K
authors.initials: K
authors.lastname: Masjedi
authors.forename: B
authors.initials: B
authors.lastname: Gruvberger
authors.forename: B
authors.initials: B
authors.lastname: Zuber
authors.forename: A-T
authors.initials: AT
authors.lastname: Karlberg
authors.forename: M
authors.initials: M
authors.lastname: Bruze
authors.forename: N
authors.initials: N
authors.lastname: Ahlborg
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006241:Haptens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010328:Patch Tests; D012717:Sesquiterpenes / Q000276:immunology*
chemical_list: D006241:Haptens; D018793:Interleukin-13; D012717:Sesquiterpenes; C002669:parthenolide; D007371:Interferon-gamma