Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse
Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse
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DOI：
10.1093/intimm/dxh073
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Bacon, KB
中科院分区：
文献类型：
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作者：
Takeshita, K;Yamasaki, T;Bacon, KB
半抗原诱导的接触性超敏反应（CHS）被认为是由辅助性T型1 （Th1）细胞介导的。然而，FITC在体内可诱发接触性过敏，体外研究表明这种反应是由th2型驱动的。我们比较了FITC或二硝基氟苯（DNFB）（一种众所周知的Th1诱导半抗原）在Balb/c小鼠、C57/B6小鼠和几种基因敲除小鼠中诱导的CHS反应，并研究了Th1/Th2细胞因子、T细胞群、嗜酸粒细胞和肥大细胞的作用。Balb/c小鼠（Th2优势株）对FITC的反应强于C57/B6小鼠（Th1优势株）。皮肤炎症以水肿和嗜酸性粒细胞增多为特征，FITC刺激后血清IgE水平升高。所有的反应都通过第二轮增敏而增强。抗tnf - α或抗极晚期抗原-4 （VLA-4）抗体部分抑制FITC-和dnfb诱导的CHS。用抗il -4抗体、抗il -5抗体、重组inf - γ或肥大细胞消耗剂48/80预处理小鼠可显著减少水肿形成，Stat6（-/-）小鼠完全免受fitc诱导的CHS，而dnlb诱导的CHS增强（Stat6(-/-)，肥大细胞消耗）或不受影响（抗il -5抗体）。此外，缺乏CD4(+) T细胞的小鼠和缺乏CD8和MHC II的小鼠对FITC的反应非常小，而单独缺乏CD8 T细胞或单独缺乏MHC II仅提供部分保护。这些发现表明MHC ii非依赖性CD4(+) T细胞和/或CD4(+) NKT细胞在体内对FITC触发的Th2反应有贡献，并使FITC诱导的CHS成为一种适合的特应性皮炎动物模型。
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.