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

Investigation of mechanisms underlying the T-cell response to the hapten 2,4-dinitrochlorobenzene
Investigation of mechanisms underlying the T-cell response to the hapten 2,4-dinitrochlorobenzene
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.
0022-202X
630-637
Pickard, Chris
d243fbd8-ea2c-4245-b64a-56b61a4f4d03
Smith, Andrew M.
6235e3c8-19d3-49d3-bf54-f28c7a0f2846
Cooper, Hywel
5d2152de-2acb-4ae4-9fca-9dd0a4de790a
Strickland, Ian
02d02a20-fc7a-480f-9dc4-9fac19e412e8
Jackson, John
ae50e8e5-c471-4097-bfc0-09d3ba8254b6
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Pickard, Chris
d243fbd8-ea2c-4245-b64a-56b61a4f4d03
Smith, Andrew M.
6235e3c8-19d3-49d3-bf54-f28c7a0f2846
Cooper, Hywel
5d2152de-2acb-4ae4-9fca-9dd0a4de790a
Strickland, Ian
02d02a20-fc7a-480f-9dc4-9fac19e412e8
Jackson, John
ae50e8e5-c471-4097-bfc0-09d3ba8254b6
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88

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), 630-637. (doi:10.1038/sj.jid.5700581). (PMID:17008874)

Record type: Article

Abstract

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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Published date: March 2007
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 195519
URI: https://eprints.soton.ac.uk/id/eprint/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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