Dierich A, Chan S H, Benoist C, Mathis D
Laboratoire de Génétique, Moléculaire des Eucaryotes du CNRS et Unité 184 de Biologie Moléculaire de l'INSERM, Institut de Chimie Biologique, Strasbourg.
Eur J Immunol. 1993 Oct;23(10):2725-8. doi: 10.1002/eji.1830231055.
The appropriate crosses of mice lacking conventional major histocompatibility complex (MHC) class I or class II molecules generate single- and double-deficient offspring. These were used as donors for skin grafts across major plus minor, or just minor, histocompatibility differences. Surprisingly, in the two circumstances, there was a rapid rejection of grafts lacking both MHC class I and class II molecules. Rejection was mediated by thymically derived CD4+ T cells of the host. We provide evidence that these T cells recognize an unconventional ligand, capable of activating a pre-formed T cell compartment but incapable of positively selecting it. The existence of this unexpected rejection phenomenon should serve to caution those aiming to engineer "universal donor" cells by simply abrogating expression of MHC class I and class II molecules.
缺乏传统主要组织相容性复合体(MHC)I类或II类分子的小鼠进行适当的杂交,可产生单缺陷和双缺陷后代。这些后代被用作皮肤移植的供体,用于跨越主要加次要或仅次要组织相容性差异的移植。令人惊讶的是,在这两种情况下,缺乏MHC I类和II类分子的移植物都被迅速排斥。排斥是由宿主胸腺来源的CD4 + T细胞介导的。我们提供的证据表明,这些T细胞识别一种非常规配体,该配体能够激活预先形成的T细胞区室,但不能对其进行阳性选择。这种意外排斥现象的存在应该提醒那些旨在通过简单地消除MHC I类和II类分子的表达来构建“通用供体细胞”的人。