Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Sep 1;98(5):1158–1164. doi: 10.1172/JCI118899

Dissection of antigenic and irritative effects of epicutaneously applied haptens in mice. Evidence that not the antigenic component but nonspecific proinflammatory effects of haptens determine the concentration-dependent elicitation of allergic contact dermatitis.

S Grabbe 1, M Steinert 1, K Mahnke 1, A Schwartz 1, T A Luger 1, T Schwarz 1
PMCID: PMC507538  PMID: 8787679

Abstract

Allergic contact dermatitis differs from most other immune reactions by its strict dose dependence during the elicitation phase. Moreover, almost all known contact allergens can also induce dose-dependent irritative dermatitis and in general only elicit allergic contact dermatitis in sensitized individuals when applied within a narrow dose range. Therefore, we hypothesized that elicitation of contact hypersensitivity (CHS) may require two signals, antigen-specific effector cell activation and a non-antigen-specific proinflammatory signal, both of which are provided by application of a sufficient dose of hapten. To dissociate these putative two signals, oxazolone-sensitized mice were ear challenged with a dose of the specific hapten which was too low to elicit CHS. At the same time, an unrelated hapten was applied in a conventional concentration to the same skin site. Whereas neither treatment alone elicited a significant CHS response, application of both compounds together resulted in a strong CHS response that was indistinguishable from that elicited by the full dose of the specific hapten. Upon coadministration of the irrelevant hapten, allergic contact dermatitis could be elicited even when the dose of the specific hapten was further reduced by a factor of 10(3). In contrast, a dose reduction of the irrelevant hapten by a factor of two resulted in the loss of the CRS response. These data indicate that non-antigen-specific effects of epicutaneously applied haptens significantly contribute to the elicitation of CHS responses and that the capacity of the hapten to evoke this proinflammatory stimulus rather than its antigenicity is responsible for the strict concentration dependence.

Full Text

The Full Text of this article is available as a PDF (229.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brasch J., Burgard J., Sterry W. Common pathogenetic pathways in allergic and irritant contact dermatitis. J Invest Dermatol. 1992 Feb;98(2):166–170. doi: 10.1111/1523-1747.ep12555804. [DOI] [PubMed] [Google Scholar]
  2. Cruz P. D., Jr, Nixon-Fulton J., Tigelaar R. E., Bergstresser P. R. Local effects of UV radiation on immunization with contact sensitizers. I. Down-regulation of contact hypersensitivity by application of TNCB to UV-irradiated skin. Photodermatol. 1988 Jun;5(3):126–132. [PubMed] [Google Scholar]
  3. Enk A. H., Angeloni V. L., Udey M. C., Katz S. I. An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin. J Immunol. 1993 May 1;150(9):3698–3704. [PubMed] [Google Scholar]
  4. Enk A. H., Katz S. I. Early molecular events in the induction phase of contact sensitivity. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1398–1402. doi: 10.1073/pnas.89.4.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gocinski B. L., Tigelaar R. E. Roles of CD4+ and CD8+ T cells in murine contact sensitivity revealed by in vivo monoclonal antibody depletion. J Immunol. 1990 Jun 1;144(11):4121–4128. [PubMed] [Google Scholar]
  6. Grabbe S., Steinbrink K., Steinert M., Luger T. A., Schwarz T. Removal of the majority of epidermal Langerhans cells by topical or systemic steroid application enhances the effector phase of murine contact hypersensitivity. J Immunol. 1995 Nov 1;155(9):4207–4217. [PubMed] [Google Scholar]
  7. Haas J., Lipkow T., Mohamadzadeh M., Kolde G., Knop J. Induction of inflammatory cytokines in murine keratinocytes upon in vivo stimulation with contact sensitizers and tolerizing analogues. Exp Dermatol. 1992 Aug;1(2):76–83. doi: 10.1111/j.1600-0625.1992.tb00075.x. [DOI] [PubMed] [Google Scholar]
  8. Kondo S., Pastore S., Shivji G. M., McKenzie R. C., Sauder D. N. Characterization of epidermal cytokine profiles in sensitization and elicitation phases of allergic contact dermatitis as well as irritant contact dermatitis in mouse skin. Lymphokine Cytokine Res. 1994 Dec;13(6):367–375. [PubMed] [Google Scholar]
  9. Kripke M. L., Morison W. L. Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice. J Invest Dermatol. 1986 May;86(5):543–549. doi: 10.1111/1523-1747.ep12355000. [DOI] [PubMed] [Google Scholar]
  10. McLelland J., Shuster S. Contact dermatitis with negative patch tests: the additive effect of allergens in combination. Br J Dermatol. 1990 May;122(5):623–630. doi: 10.1111/j.1365-2133.1990.tb07284.x. [DOI] [PubMed] [Google Scholar]
  11. McLelland J., Shuster S., Matthews J. N. 'Irritants' increase the response to an allergen in allergic contact dermatitis. Arch Dermatol. 1991 Jul;127(7):1016–1019. [PubMed] [Google Scholar]
  12. Montelius J., Wahlkvist H., Boman A., Fernström P., Gråbergs L., Wahlberg J. E. Experience with the murine local lymph node assay: inability to discriminate between allergens and irritants. Acta Derm Venereol. 1994 Jan;74(1):22–27. doi: 10.2340/00015555742227. [DOI] [PubMed] [Google Scholar]
  13. Schwarz A., Grabbe S., Aragane Y., Sandkuhl K., Riemann H., Luger T. A., Kubin M., Trinchieri G., Schwarz T. Interleukin-12 prevents ultraviolet B-induced local immunosuppression and overcomes UVB-induced tolerance. J Invest Dermatol. 1996 Jun;106(6):1187–1191. doi: 10.1111/1523-1747.ep12347944. [DOI] [PubMed] [Google Scholar]
  14. Schwarz A., Grabbe S., Riemann H., Aragane Y., Simon M., Manon S., Andrade S., Luger T. A., Zlotnik A., Schwarz T. In vivo effects of interleukin-10 on contact hypersensitivity and delayed-type hypersensitivity reactions. J Invest Dermatol. 1994 Aug;103(2):211–216. doi: 10.1111/1523-1747.ep12393073. [DOI] [PubMed] [Google Scholar]
  15. Ullrich S. E. The role of epidermal cytokines in the generation of cutaneous immune reactions and ultraviolet radiation-induced immune suppression. Photochem Photobiol. 1995 Sep;62(3):389–401. doi: 10.1111/j.1751-1097.1995.tb02359.x. [DOI] [PubMed] [Google Scholar]
  16. Willis C. M., Young E., Brandon D. R., Wilkinson J. D. Immunopathological and ultrastructural findings in human allergic and irritant contact dermatitis. Br J Dermatol. 1986 Sep;115(3):305–316. doi: 10.1111/j.1365-2133.1986.tb05745.x. [DOI] [PubMed] [Google Scholar]
  17. Zheng H., Fletcher D., Kozak W., Jiang M., Hofmann K. J., Conn C. A., Soszynski D., Grabiec C., Trumbauer M. E., Shaw A. Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice. Immunity. 1995 Jul;3(1):9–19. doi: 10.1016/1074-7613(95)90154-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES