Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse

Int Immunol. 2004 May;16(5):685-95. doi: 10.1093/intimm/dxh073. Epub 2004 Mar 29.

Abstract

Contact hypersensitivity (CHS) induced by a hapten is thought to be mediated by T helper type 1 (Th1) cells. However, FITC can induce contact allergy in vivo, and in vitro studies suggest that this response is Th2-type driven. We compared CHS reactions induced by FITC or dinitrofluorobenzene (DNFB), a well-known Th1 inducing hapten, in Balb/c mice, C57/B6 mice, and several gene knock-out mice, and investigated the role of Th1/Th2 cytokines, T cell populations, eosinophils, and mast cells. Balb/c mice (Th2 dominant strain) had a stronger response to FITC than C57/B6 mice (Th1 dominant strain). The skin inflammation was characterized by edema and eosinophilia, and serum IgE levels were elevated following FITC challenge. All responses were enhanced by a second round of sensitization. Anti-TNF-alpha or anti-very late antigen-4 (VLA-4) antibody partly inhibited both FITC- and DNFB-induced CHS. Pretreatment of mice with anti-IL-4 antibody, anti-IL-5 antibody, recombinant INF-gamma, or the mast-cell depleting agent 48/80 significantly diminished edema formation, and Stat6(-/-) mice were fully protected from FITC-induced CHS, while DNFB-induced CHS was enhanced (Stat6(-/-), mast cell depletion) or not affected (anti-IL-5 antibody). Further, mice lacking CD4(+) T cells and mice lacking both CD8 and MHC II showed very little reaction at all to FITC, while the absence of CD8 T cells alone or MHC II alone conferred partial protection only. These findings indicate a contribution of MHC II-independent CD4(+) T cells and/or CD4(+) NKT cells to the Th2 response triggered by FITC in vivo, and makes FITC-induced CHS a suitable animal model for atopic dermatitis.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Dermatitis, Allergic Contact / immunology*
  • Dermatitis, Allergic Contact / pathology
  • Eosinophil Peroxidase / metabolism
  • Female
  • Fluorescein-5-isothiocyanate / toxicity*
  • Gene Deletion
  • Genes, MHC Class I / genetics
  • Genes, MHC Class II* / genetics
  • Haptens / immunology*
  • Immunoglobulin E / immunology
  • Integrin alpha4beta1 / immunology
  • Interleukin-4 / physiology*
  • Interleukin-5 / immunology
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nitrosamines / toxicity
  • STAT6 Transcription Factor
  • Skin / pathology
  • Th2 Cells / immunology
  • Trans-Activators / physiology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Haptens
  • Integrin alpha4beta1
  • Interleukin-5
  • Nitrosamines
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Immunoglobulin E
  • N,N-dinitrosohomopiperazine
  • Eosinophil Peroxidase
  • Fluorescein-5-isothiocyanate