Volume 4 Supplement 3

6th Drug Hypersensitivity Meeting (DHM 6)

Open Access

Detection of interleukin-22 secreting T-cells in piperacillin hypersensitive patients with cystic fibrosis

  • Andrew Sullivan1,
  • Eryi Wang1,
  • John Farrell1,
  • Paul Whitaker2,
  • Daniel Peckham2,
  • B Kevin Park1 and
  • Dean Naisbitt1
Clinical and Translational Allergy20144(Suppl 3):P108

https://doi.org/10.1186/2045-7022-4-S3-P108

Published: 18 July 2014

Delayed-type cutaneous drug hypersensitivity is a T-cell mediated disease; the spectrum of conditions has been classified according to the phenotype and function of drug antigen-specific T-cells sub-sets. Importantly, this classification does not take into account tissue-specific cytokines such as interleukin-17 and interleukin-22. Both of these cytokines have been shown to play a role in numerous physiological and pathological processes. For example, elevated levels have been detected in patients with psoriasis and allergic contact dermatitis. To investigate this, we have focused on piperacillin, a β-lactam antibiotic used for the treatment of pulmonary exacerbations in patients with cystic fibrosis. Unfortunately hypersensitivity reactions (mean onset = 9.1 days; symptoms include maculopapular rash, fever and/or flu-like symptoms) to this drug develop in 26-50% of treated patients. Piperacillin-specific T-cell clones were generated from 3 lymphocyte transformation test positive hypersensitive patients and 4 healthy donors, following priming of naïve T-cells against piperacillin-exposed dendritic cells, to characterize T-cell phenotype (CD and chemokine receptor expression) and function (proliferation and secretion of cytokines/cytolytic molecules [IFNγ, 13, 17, 22 by ELIspot]). Seventy six CD4+ and CD8+ clones were isolated from the hypersensitive patients and shown to proliferate in the presence of piperacillin. Drug stimulation was associated with the secretion of IFN-γ and IL13 from all clones. IL-22 secretion was detected from 64% and 75% of the CD4+ and CD8+ clones, respectively. In contrast, IL17 was not detected. Naïve T-cells co-cultured with piperacillin and autologous dendritic cells showed concentration-dependent proliferation and cytokine (IFNγ, IL13 and IL22) secretion. CD4+ and CD8+ clones generated from the primed T-cells also secreted IFNγ, IL13 and IL22 (CD4+ 50%, CD8+ 67%) following piperacillin stimulation. CCR1, CCR4 and CCR10 were expressed on all clones. Other chemokine receptors expressed on a limited number of clones included CXCR3, CXCR6, CCR2 and CCR9. In conclusion, these data show the involvement of IL22 secreting T-cells in the pathogenesis of piperacillin hypersensitivity reactions in patients with cystic fibrosis.

Authors’ Affiliations

(1)
Centre for Drug Safety Science, University Of Liverpool
(2)
St James' Hospital, Regional Adult Cystic Fibrosis Unit

Copyright

© Sullivan et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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