Cellular and molecular mechanisms in the induction phase of contact sensitivity.
During the induction phase of contact sensitivity, hapten-specific Th1 cells are primed by epidermal Langerhans cells. These Langerhans cells present hapten on MHC class II molecules and provide costimulatory signals. This presentation discusses the induction of cytokines in Langerhans cells and keratinocytes by haptens and their regulatory effects on contact sensitivity. Haptens were painted on the skin of normal BALB/c mice and epidermal cells were prepared at various times thereafter. Langerhans cell-derived interleukin (IL)-1 beta mRNA was observed as early as 15 min after hapten paining. In keratinocytes, tumor necrosis factor-alpha, IL-1 alpha, IP-10, MIP-2 and IL-10 were found to be up-regulated. IL-1 beta appeared to be a 'master' cytokine since it was able to mimic the effects of haptens, such as the increase of MHC class II expression in Langerhans cells and activation of the cytokine cascade. Injection of anti-IL-1 beta monoclonal antibody prior to hapten application completely prevented epicutaneous sensitization. In vivo application of IL-10 by intradermal injection prior to epicutaneous application of TNCB induced antigen-specific tolerance and impeded the induction of proinflammatory cytokines.
Knop
J
J
Department of Dermatology, University of Mainz, Germany.
Enk
A H
AH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D017951:Antigen Presentation; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D004136:Dinitrobenzenes / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000276:immunology / Q000633:toxicity; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000633:toxicity; D006241:Haptens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009578:Nitrobenzenes / Q000494:pharmacology; D010853:Picryl Chloride / Q000276:immunology / Q000633:toxicity
D000911:Antibodies, Monoclonal; D016207:Cytokines; D004136:Dinitrobenzenes; D004137:Dinitrochlorobenzene; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D009578:Nitrobenzenes; C028328:1,2-dichloro-4-nitrobenzene; D004139:Dinitrofluorobenzene; C010936:2,4-dinitrothiocyanatobenzene; D010853:Picryl Chloride