Th1 and type 1 cytotoxic T cells dominate responses in T-bet overexpression transgenic mice that develop contact dermatitis
Th1 and type 1 cytotoxic T cells dominate responses in T-bet overexpression transgenic mice that develop contact dermatitis
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DOI：
10.4049/jimmunol.178.1.605
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
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作者：
Ishizaki, Kazusa;Yamada, Akiko;Takahashi, Satoru
人类接触性皮炎和动物模型接触性超敏反应（CHS）是由半抗原特异性T细胞介导的迟发型超敏反应。最近，已经清楚的是，CD 4（+）Th 1和CD 8（+）1型细胞毒性T（Tc 1）细胞都可以在CHS反应中作为效应子。T-bet已被证明在Th 1和Tc 1细胞分化中发挥重要作用，但对其在CHS中的作用知之甚少。在本研究中，我们使用T-bet转基因（Tg）的C57 BL/6小鼠来解决这个问题。这些在T淋巴细胞中过表达T-bet的Tg小鼠发生皮炎，其特征在于在没有体毛的区域中皮肤肿胀、肿胀和鳞状。皮肤组织学显示表皮角化过度、中性粒细胞和淋巴细胞浸润，与接触性皮炎相似。Tg小鼠中T-bet过表达导致Th 1 IG（IgG 2a）产生升高和Th 2 IG（IgG 1）产生降低。细胞内细胞因子分析表明，IFN-γ在Th 1和Tc 1细胞中均增加。此外，Tg小鼠对用于CHS诱导的2，4-二硝基氟苯有过敏反应。这些结果表明，T-bet的表达水平可能在接触性皮炎的发展中发挥重要作用，这些Tg小鼠应该是一个有用的模型接触性皮炎。
Contact dermatitis in humans and contact hypersensitivity (CHS) in animal models are delayed-type hypersensitivity reactions mediated by hapten-specific T cells. Recently, it has become clear that both CD4(+) Th1 and CD8(+) type 1 cytotoxic T (Tc1) cells can act as effectors in CHS reactions. T-bet has been demonstrated to play an important role in Th1 and Tc1 cell differentiation, but little is known about its contribution to CHS. In the present study, we used C57BL/6 mice transgenic (Tg) for T-bet to address this issue. These Tg mice, which overexpressed T-bet in their T lymphocytes, developed dermatitis characterized by swollen, flaky, and scaly skin in regions without body hair. Skin histology showed epidermal hyperkeratosis, neutrophil, and lymphocyte infiltration similar to that seen in contact dermatitis. T-bet overexpression in Tg mice led to elevated Th1 Ig (IgG2a) and decreased Th2 Ig (IgG1) production. Intracellular cytokine analyses demonstrated that IFN-gamma was increased in both Th1 and Tc1 cells. Furthermore, Tg mice had hypersensitive responses to 2,4-dinitrofluorobenzene, which is used for CHS induction. These results suggest that the level of expression of T-bet might play an important role in the development of contact dermatitis and that these Tg mice should be a useful model for contact dermatitis.