Chemical carcinogens and antigens induce immune suppression via Langerhans' cell depletion.
The ability of the chemical carcinogen dimethylbenz(a)anthracene (DMBA) to deplete Langerhans' cells (LC) from murine skin is crucial to the development of antigen-specific suppression. This depletion is a consequence of the LC recognizing the DMBA as antigenic and migrating to the draining lymph nodes to attempt to elicit T-cell activation. This depletion also occurred following exposure to high doses of the contact sensitizers 2,4-dinitrofluorobenzene (DNFB), 2,4,6-trinitrochlorobenzene (TNCB) and fluorescein isothiocyanate (FITC). However, LC depletion was not significant at lower doses, even though these doses were sufficient to induce strong contact sensitivity responses. Application of the contact sensitizer, DNFB, through skin depleted of LC (by pretreatment with either the carcinogen DMBA or the antigen TNCB) failed to induce contact sensitivity. This immune non-responsiveness was antigen specific, and could be transferred by spleen cells to naive mice, which were unable to respond to DNFB. Mouse skin treated with doses of TNCB, that did not cause LC depletion but still induced a normal contact hypersensitivity, retained its ability to initiate a normal immune response to DNFB. Together these findings demonstrate that carcinogens share some properties with antigens as they both cause LC depletion and interact with the immune system. Furthermore, it is this LC depletion, rather than carcinogen treatment, that is a critical factor which leaves the skin immunologically compromised and favours the induction of antigen-specific suppression.
Woods
G M
GM
Division of Pathology, University of Tasmania, Hobart, Australia.
Qu
M
M
Ragg
S J
SJ
Muller
H K
HK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002452:Cell Count; D002465:Cell Movement; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D007108:Immune Tolerance; D007801:Langerhans Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010853:Picryl Chloride / Q000494:pharmacology
D000941:Antigens; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D004139:Dinitrofluorobenzene; D016650:Fluorescein-5-isothiocyanate; D010853:Picryl Chloride