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.
Pickard
Chris
C
Dermatopharmacology Unit, Southampton General Hospital, Southampton, UK.
Smith
Andrew M
AM
Cooper
Hywel
H
Strickland
Ian
I
Jackson
John
J
Healy
Eugene
E
Friedmann
Peter S
PS
D000328:Adult; D000938:Antigen-Presenting Cells / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D004137:Dinitrochlorobenzene / Q000494:pharmacology*; D005260:Female; D006241:Haptens / Q000737:chemistry*; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects*; D015262:Xenobiotics / Q000737:chemistry
D004137:Dinitrochlorobenzene; D006241:Haptens; D015262:Xenobiotics; D016753:Interleukin-10; D007371:Interferon-gamma