Uehira M, Matsuda H, Nakamura A, Nishimoto H
Shionogi Institute for Medical Science, Osaka, Japan.
J Invest Dermatol. 1998 May;110(5):740-5. doi: 10.1046/j.1523-1747.1998.00179.x.
Interleukin (IL)-7 transgenic mice, which we established previously, developed severe dermatitis characterized by massive infiltration of gammadelta T cells in the dermal lesion. To fully understand the pathology of this intriguing skin disease, we examined several immunologic features of dermis infiltrating lymphocytes from the lesional skin of IL-7 transgenic mice. We observed a moderate response to mitogens, a poor response to alloantigens, and the absence of cytotoxic activities to several tumor cell lines and skin derived cells regardless of the presence of IL-2 or IL-7. On the other hand, dermis infiltrating lymphocytes could proliferate with exogenous IL-2 and IL-7. Moreover, reverse transcriptase polymerase chain reaction and fluorescence activated cell sorter analysis revealed that dermis infiltrating lymphocytes expressed various cytokines including IL-4 and IL-7, and several activation markers for T cells (CD44, CD69, IL-2R alpha), in addition to IL-7R alpha. In the sera of the affected mice, hyper epsilon-globulinemia was observed. These findings suggested that dermis infiltrating lymphocytes proliferated in an activated state in the skin lesion in an autocrine and/or paracrine manner and produced Th2 type cytokines that might evoke immunologic abnormalities. This study and previous findings suggest that IL-7 transgenic mouse with dermatitis offer the potential of serving as a useful tool for investigating the immunologic role of cutaneous gammadelta T cells, especially their participation in IgE production in vivo.
我们先前构建的白细胞介素(IL)-7转基因小鼠出现了严重的皮炎,其特征为皮肤病变处有大量γδT细胞浸润。为了全面了解这种有趣皮肤病的病理,我们检测了来自IL-7转基因小鼠病变皮肤真皮浸润淋巴细胞的几种免疫学特征。我们观察到这些细胞对丝裂原的反应适度,对同种异体抗原的反应较差,并且无论是否存在IL-2或IL-7,对几种肿瘤细胞系和皮肤来源细胞均无细胞毒性活性。另一方面,真皮浸润淋巴细胞可通过外源性IL-2和IL-7进行增殖。此外,逆转录聚合酶链反应和荧光激活细胞分选分析显示,真皮浸润淋巴细胞除了表达IL-7Rα外,还表达包括IL-4和IL-7在内的多种细胞因子,以及几种T细胞激活标志物(CD44、CD69、IL-2Rα)。在患病小鼠的血清中,观察到高ε球蛋白血症。这些发现表明,真皮浸润淋巴细胞在皮肤病变中以自分泌和/或旁分泌方式在激活状态下增殖,并产生可能引发免疫异常的Th2型细胞因子。本研究和先前的发现表明,患有皮炎的IL-7转基因小鼠有可能成为研究皮肤γδT细胞免疫作用,特别是它们在体内参与IgE产生的有用工具。