The lipophilic hapten parthenolide induces interferon-γ and interleukin-13 production by peripheral blood-derived CD8+ T cells from contact allergic subjects in vitro

Authors


  • Conflicts of interest
    H.W., K.M., B.Z. and N.A. are or have been employees at Mabtech AB, a Swedish biotech company from which monoclonal antibody reagents used in the study were obtained. No author owns shares or stocks in the company.

  • H.W. and K.M. contributed equally to the study.

Niklas Ahlborg.
E-mail: niklas@mabtech.com

Abstract

Summary 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.

Objectives  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.

Patients and methods  Ten allergic subjects with strong (= 6), moderate (= 2), or weak (= 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)-γ, interleukin (IL)-2, IL-4, IL-5 (< 0·05 for all) and IL-13 (< 0·01). The responses manifested by T-cell type 1 (IFN-γ 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-γ- 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.

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