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Investigation of mechanisms underlying the T-cell response to the hapten 2,4-dinitrochlorobenzene

Record type: Article

T-cell mediated contact sensitization by small molecular weight xenobiotics results in significant morbidity and absences from work. To be recognized by T-cells, xenobiotics must act as haptens, becoming protein-bound. At present, the requirement for processing and presentation of xenobiotics, the nature of the T-cell responses to them and the mechanisms that confer individual susceptibility in humans are unclear. We have investigated the T-cell response to the hapten 2,4-dinitrochlorobenzene (DNCB) which can sensitize all immunocompetent people. Fourteen healthy adults were sensitized with DNCB; 11 demonstrated positive T-cell responses to the chemical in vitro. Responding cells were of both CD4+ and CD8+ subsets, of Th1 and Tc1 phenotypes, producing high levels of IFN-gamma and low levels of IL-10. DNCB-specific T-cell clones were raised from 2 subjects, which in the presence of fixed and unfixed autologous Epstein-Barr virus transformed B cells as antigen-presenting-cells (APC), demonstrated that the chemical requires metabolic processing by the APC in order to initiate the T-cell response. Intracellular-reduced glutathione is consumed in detoxication of DNCB, leaving residual non-detoxified DNCB free to bind to proteins. The results suggest that DNCB forms multiple haptens with intracellular and extracellular proteins leading to Th1 and Tc1 responses in individuals exposed to this compound.

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Pickard, Chris, Smith, Andrew M., Cooper, Hywel, Strickland, Ian, Jackson, John, Healy, Eugene and Friedmann, Peter S. (2007) Investigation of mechanisms underlying the T-cell response to the hapten 2,4-dinitrochlorobenzene Journal of Investigative Dermatology, 127, (3), pp. 630-637. (doi:10.1038/sj.jid.5700581). (PMID:17008874).

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Published date: March 2007
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 195519
ISSN: 0022-202X
PURE UUID: c21a21c0-09f4-4c6a-b225-07d3c386513c

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Date deposited: 22 Aug 2011 15:24
Last modified: 18 Jul 2017 11:24

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Author: Chris Pickard
Author: Andrew M. Smith
Author: Hywel Cooper
Author: Ian Strickland
Author: John Jackson
Author: Eugene Healy
Author: Peter S. Friedmann

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