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

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.

• Authors: Keisuke Takeshita, Tsugiko Yamasaki, Shizuo Akira, Florian Gantner, Kevin B Bacon
• Journal: International immunology (Int Immunol) Vol. 16 Issue 5 Pg. 685-95 (May 2004) ISSN: 0953-8178 [Print] England
• PMID: 15096484 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Dermatitis, Allergic Contact (immunology, 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)