Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse.
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.
Takeshita
Keisuke
K
Bayer Yakuhin, Ltd., Research Center Kyoto, Department of Respiratory Diseases Research, Japan.
Yamasaki
Tsugiko
T
Akira
Shizuo
S
Gantner
Florian
F
Bacon
Kevin B
KB
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D047209:Eosinophil Peroxidase / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000633:toxicity*; D017353:Gene Deletion; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D006241:Haptens / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000276:immunology; D015847:Interleukin-4 / Q000502:physiology*; D015848:Interleukin-5 / Q000276:immunology; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009602:Nitrosamines / Q000633:toxicity; D050800:STAT6 Transcription Factor; D012867:Skin / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D006241:Haptens; D039041:Integrin alpha4beta1; D015848:Interleukin-5; D009602:Nitrosamines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; C037528:N,N-dinitrosohomopiperazine; D047209:Eosinophil Peroxidase; D016650:Fluorescein-5-isothiocyanate