Keratinocyte expression of B7-1 in transgenic mice amplifies the primary immune response to cutaneous antigens.
Keratinocyte expression of B7-1 in transgenic mice amplifies the primary immune response to cutaneous antigens.
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转基因小鼠中 B7-1 的角质形成细胞表达增强了对皮肤抗原的初级免疫反应。
DOI：
10.1073/pnas.91.26.12780
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发表时间：
1994
影响因子：
11.1
通讯作者：
Kupper,TS
中科院分区：
文献类型：
--
作者：
Williams,IR;Ort,RJ;Kupper,TS
静止的表皮角质形成细胞不表达B7-1和其他已知的具有共刺激活性的CD 28反配体。角质形成细胞上这些共刺激因子的缺乏与它们优先诱导T细胞无反应性而不是T细胞活化的能力相关。为了验证表达CD 28配体的角质形成细胞是皮肤中T细胞介导的免疫应答的更有效诱导剂的假设，我们制备了转基因小鼠，其中通过使用人K14启动子将B7-1共刺激因子的表达靶向基底角质形成细胞。来自K14/B7-1转基因系的角质形成细胞表达高水平的表面B7-1。在转基因小鼠皮肤中没有观察到自发性炎症变化，但对这些小鼠表皮应用接触致敏剂引起了比对照组更强的原发性耳肿胀反应。在转基因小鼠中，初始半抗原应用的位点对将半抗原重新应用于远程皮肤位点的反应也强烈得多。当通过流式细胞术分析时，来自转基因小鼠的表皮细胞悬浮液含有正常数量的朗格汉斯细胞和树突状表皮T细胞。用干扰素γ对转基因小鼠进行全身治疗，诱导角质形成细胞上高水平的II类主要组织相容性复合物表达，但不足以引发炎症反应。我们的结论是，组成型表达的B7-1分子在体内的一个非专业的抗原呈递细胞本身并不足以引发炎症的变化，但B7-1的表达放大暴露后的非自身抗原提出的B7-1表达细胞的宿主免疫反应。
Resting epidermal keratinocytes do not express B7-1 and other known CD28 counterligands with costimulatory activity. The absence of these costimulators on keratinocytes correlates with their ability to preferentially induce T-cell anergy instead of T-cell activation. To test the hypothesis that keratinocytes expressing a CD28 counterligand would be more effective inducers of T-cell-mediated immune responses in skin, we prepared transgenic mice in which expression of the B7-1 costimulator was targeted to basal keratinocytes by using the human K14 promoter. Keratinocytes from the K14/B7-1 transgenic line expressed high levels of surface B7-1. No spontaneous inflammatory changes were seen in transgenic skin, but epicutaneous application of contact sensitizers to these mice elicited a stronger primary ear swelling response than in controls. Sites of initial hapten application in transgenic mice also responded much more strongly to reapplication of hapten to a remote cutaneous site. Epidermal cell suspensions from transgenic mice contained normal numbers of Langerhans cells and dendritic epidermal T cells when analyzed by flow cytometry. Systemic treatment of the transgenic mice with interferon gamma induced high levels of class II major histocompatibility complex expression on keratinocytes but was not sufficient to initiate an inflammatory response. We conclude that the constitutive expression of the B7-1 molecule in vivo on a nonprofessional antigen-presenting cell is not by itself sufficient to trigger inflammatory changes, but B7-1 expression amplifies the host immune responses after exposure to nonself antigens presented by B7-1-expressing cells.